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Angiogenesis

Erschienen in:

18.03.2022 | Review Paper

Molecular mechanisms of coronary microvascular endothelial dysfunction in diabetes mellitus: focus on mitochondrial quality surveillance

verfasst von: Danan Sun, Jin Wang, Sam Toan, David Muid, Ruibing Li, Xing Chang, Hao Zhou

Erschienen in: Angiogenesis | Ausgabe 3/2022

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Abstract

Coronary microvascular endothelial dysfunction is both a culprit and a victim of diabetes, and can accelerate diabetes-related microvascular and macrovascular complications by promoting vasoconstrictive, pro-inflammatory and pro-thrombotic responses. Perturbed mitochondrial function induces oxidative stress, disrupts metabolism and activates apoptosis in endothelial cells, thus exacerbating the progression of coronary microvascular complications in diabetes. The mitochondrial quality surveillance (MQS) system responds to stress by altering mitochondrial metabolism, dynamics (fission and fusion), mitophagy and biogenesis. Dysfunctional mitochondria are prone to fission, which generates two distinct types of mitochondria: one with a normal and the other with a depolarized mitochondrial membrane potential. Mitochondrial fusion and mitophagy can restore the membrane potential and homeostasis of defective mitochondrial fragments. Mitophagy-induced decreases in the mitochondrial population can be reversed by mitochondrial biogenesis. MQS abnormalities induce pathological mitochondrial fission, delayed mitophagy, impaired metabolism and defective biogenesis, thus promoting the accumulation of unhealthy mitochondria and the activation of mitochondria-dependent apoptosis. In this review, we examine the effects of MQS on mitochondrial fitness and explore the association of MQS disorders with coronary microvascular endothelial dysfunction in diabetes. We also discuss the potential to treat diabetes-related coronary microvascular endothelial dysfunction using novel MQS-altering drugs.

Joslin EP (2021) The prevention of diabetes mellitus. JAMA 325(2):190. https://doi.org/10.1001/jama.2020.17738CrossRef

American Diabetes Association (2009) Diagnosis and classification of diabetes mellitus. Diabetes Care 32(Suppl 1):S62–S67. https://doi.org/10.2337/dc09-S062CrossRefPubMedCentral

Forbes JM, Cooper ME (2013) Mechanisms of diabetic complications. Physiol Rev 93(1):137–188. doi:https://doi.org/10.1152/physrev.00045.2011CrossRefPubMed

Escaned J, Lerman LO (2020) Coronary microcirculation and hypertensive heart failure. Eur Heart J 41(25):2376–2378. doi:https://doi.org/10.1093/eurheartj/ehaa437CrossRefPubMed

Lüscher TF (2018) Assessing myocardial ischaemia in epicardial coronaries and the microcirculation. Eur Heart J 39(46):4047–4050. doi:https://doi.org/10.1093/eurheartj/ehy816CrossRefPubMed

Taqueti VR, Di Carli MF (2018) Coronary microvascular disease pathogenic mechanisms and therapeutic options: JACC state-of-the-art review. J Am Coll Cardiol 72(21):2625–2641. https://doi.org/10.1016/j.jacc.2018.09.042CrossRefPubMedPubMedCentral

Vancheri F, Longo G, Vancheri S, Henein M (2020) Coronary microvascular dysfunction. J Clin Med. https://doi.org/10.3390/jcm9092880CrossRefPubMedPubMedCentral

Cuijpers I, Simmonds SJ, van Bilsen M, Czarnowska E, González Miqueo A, Heymans S, Kuhn AR, Mulder P, Ratajska A, Jones EAV, Brakenhielm E (2020) Microvascular and lymphatic dysfunction in HFpEF and its associated comorbidities. Basic Res Cardiol 115(4):39. doi:https://doi.org/10.1007/s00395-020-0798-yCrossRefPubMedPubMedCentral

Paulus WJ, Tschöpe C (2013) A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. J Am Coll Cardiol 62(4):263–271. doi:https://doi.org/10.1016/j.jacc.2013.02.092CrossRefPubMed

10.

Jia G, Hill MA, Sowers JR (2018) Diabetic Cardiomyopathy: An Update of Mechanisms Contributing to This Clinical Entity. Circul Res 122(4):624–638. doi:https://doi.org/10.1161/circresaha.117.311586CrossRef

11.

Shivu GN, Phan TT, Abozguia K, Ahmed I, Wagenmakers A, Henning A, Narendran P, Stevens M, Frenneaux M (2010) Relationship between coronary microvascular dysfunction and cardiac energetics impairment in type 1 diabetes mellitus. Circulation 121(10):1209–1215. doi:https://doi.org/10.1161/circulationaha.109.873273CrossRefPubMed

12.

Kibel A, Selthofer-Relatic K, Drenjancevic I, Bacun T, Bosnjak I, Kibel D, Gros M (2017) Coronary microvascular dysfunction in diabetes mellitus. J Int Med Res 45(6):1901–1929. doi:https://doi.org/10.1177/0300060516675504CrossRefPubMedPubMedCentral

13.

Akbari M, Kirkwood TBL, Bohr VA (2019) Mitochondria in the signaling pathways that control longevity and health span. Ageing Res Rev 54:100940. doi:https://doi.org/10.1016/j.arr.2019.100940CrossRefPubMedPubMedCentral

14.

Kalyanaraman B, Cheng G, Hardy M, Ouari O, Lopez M, Joseph J, Zielonka J, Dwinell MB (2018) A review of the basics of mitochondrial bioenergetics, metabolism, and related signaling pathways in cancer cells: Therapeutic targeting of tumor mitochondria with lipophilic cationic compounds. Redox Biol 14:316–327. doi:https://doi.org/10.1016/j.redox.2017.09.020CrossRefPubMed

15.

Wang J, Toan S, Zhou H (2020) New insights into the role of mitochondria in cardiac microvascular ischemia/reperfusion injury. Angiogenesis 23(3):299–314. doi:https://doi.org/10.1007/s10456-020-09720-2CrossRefPubMed

16.

Apostolova N, Iannantuoni F, Gruevska A, Muntane J, Rocha M, Victor VM (2020) Mechanisms of action of metformin in type 2 diabetes: Effects on mitochondria and leukocyte-endothelium interactions. Redox Biol 34:101517. doi:https://doi.org/10.1016/j.redox.2020.101517CrossRefPubMedPubMedCentral

17.

Chowdhury AR, Zielonka J, Kalyanaraman B, Hartley RC, Murphy MP, Avadhani NG (2020) Mitochondria-targeted paraquat and metformin mediate ROS production to induce multiple pathways of retrograde signaling: a dose-dependent phenomenon. Redox Biol 36:101606. https://doi.org/10.1016/j.redox.2020.101606CrossRefPubMedPubMedCentral

18.

Zhu H, Toan S, Mui D, Zhou H (2021) Mitochondrial quality surveillance as a therapeutic target in myocardial infarction. Acta Physiol 231(3):e13590. https://doi.org/10.1111/apha.13590CrossRef

19.

Zhou H, Ren J, Toan S, Mui D (2021) Role of mitochondrial quality surveillance in myocardial infarction: From bench to bedside. Ageing Res Rev 66:101250. doi:https://doi.org/10.1016/j.arr.2020.101250CrossRefPubMed

20.

Cho HM, Ryu JR, Jo Y, Seo TW, Choi YN, Kim JH, Chung JM, Cho B, Kang HC, Yu SW, Yoo SJ, Kim H, Sun W (2019) Drp1-Zip1 Interaction Regulates Mitochondrial Quality Surveillance System. Mol Cell 73(2):364–376e368. doi:https://doi.org/10.1016/j.molcel.2018.11.009CrossRefPubMed

21.

Guarini G, Huqi A, Morrone D, Capozza P, Todiere G, Marzilli M (2014) Pharmacological approaches to coronary microvascular dysfunction. Pharmacol Ther 144(3):283–302. doi:https://doi.org/10.1016/j.pharmthera.2014.06.008CrossRefPubMed

22.

Tabit CE, Chung WB, Hamburg NM, Vita JA (2010) Endothelial dysfunction in diabetes mellitus: molecular mechanisms and clinical implications. Rev Endocr Metab Disord 11(1):61–74. doi:https://doi.org/10.1007/s11154-010-9134-4CrossRefPubMedPubMedCentral

23.

Chang X, Lochner A, Wang HH, Wang S, Zhu H, Ren J, Zhou H (2021) Coronary microvascular injury in myocardial infarction: perception and knowledge for mitochondrial quality control. Theranostics 11(14):6766–6785. doi:https://doi.org/10.7150/thno.60143CrossRefPubMedPubMedCentral

24.

Chen WW, Freinkman E, Wang T, Birsoy K, Sabatini DM (2016) Absolute Quantification of Matrix Metabolites Reveals the Dynamics of Mitochondrial Metabolism. Cell 166(5):1324–1337e1311. doi:https://doi.org/10.1016/j.cell.2016.07.040CrossRefPubMedPubMedCentral

25.

Qiao K, Liu Y, Xu Z, Zhang H, Zhang H, Zhang C, Chang Z, Lu X, Li Z, Luo C, Liu Y, Yang C, Sun T (2020) RNA m6A methylation promotes the formation of vasculogenic mimicry in hepatocellular carcinoma via Hippo pathway. Angiogenesis. doi:https://doi.org/10.1007/s10456-020-09744-8CrossRefPubMed

26.

Ollauri-Ibáñez C, Núñez-Gómez E, Egido-Turrión C, Silva-Sousa L, Díaz-Rodríguez E, Rodríguez-Barbero A, López-Novoa JM, Pericacho M (2020) Continuous endoglin (CD105) overexpression disrupts angiogenesis and facilitates tumor cell metastasis. Angiogenesis 23(2):231–247. doi:https://doi.org/10.1007/s10456-019-09703-yCrossRefPubMedPubMedCentral

27.

Nguyen QL, Okuno N, Hamashima T, Dang ST, Fujikawa M, Ishii Y, Enomoto A, Maki T, Nguyen HN, Nguyen VT, Fujimori T, Mori H, Andrae J, Betsholtz C, Takao K, Yamamoto S, Sasahara M (2020) Vascular PDGFR-alpha protects against BBB dysfunction after stroke in mice. Angiogenesis. doi:https://doi.org/10.1007/s10456-020-09742-wCrossRefPubMedPubMedCentral

28.

Nawaz MI, Rezzola S, Tobia C, Coltrini D, Belleri M, Mitola S, Corsini M, Sandomenico A, Caporale A, Ruvo M, Presta M (2020) D-Peptide analogues of Boc-Phe-Leu-Phe-Leu-Phe-COOH induce neovascularization via endothelial N-formyl peptide receptor 3. Angiogenesis 23(3):357–369. doi:https://doi.org/10.1007/s10456-020-09714-0CrossRefPubMed

29.

Nakamoto S, Ito Y, Nishizawa N, Goto T, Kojo K, Kumamoto Y, Watanabe M, Majima M (2020) Lymphangiogenesis and accumulation of reparative macrophages contribute to liver repair after hepatic ischemia-reperfusion injury. Angiogenesis 23(3):395–410. doi:https://doi.org/10.1007/s10456-020-09718-wCrossRefPubMed

30.

Moon EH, Kim YH, Vu PN, Yoo H, Hong K, Lee YJ, Oh SP (2020) TMEM100 is a key factor for specification of lymphatic endothelial progenitors. Angiogenesis 23(3):339–355. doi:https://doi.org/10.1007/s10456-020-09713-1CrossRefPubMed

31.

Pennathur S, Heinecke JW (2007) Oxidative stress and endothelial dysfunction in vascular disease. Curr Diab Rep 7(4):257–264. doi:https://doi.org/10.1007/s11892-007-0041-3CrossRefPubMed

32.

De Bock K, Georgiadou M, Schoors S, Kuchnio A, Wong BW, Cantelmo AR, Quaegebeur A, Ghesquière B, Cauwenberghs S, Eelen G, Phng LK, Betz I, Tembuyser B, Brepoels K, Welti J, Geudens I, Segura I, Cruys B, Bifari F, Decimo I, Blanco R, Wyns S, Vangindertael J, Rocha S, Collins RT, Munck S, Daelemans D, Imamura H, Devlieger R, Rider M, Van Veldhoven PP, Schuit F, Bartrons R, Hofkens J, Fraisl P, Telang S, Deberardinis RJ, Schoonjans L, Vinckier S, Chesney J, Gerhardt H, Dewerchin M, Carmeliet P (2013) Role of PFKFB3-driven glycolysis in vessel sprouting. Cell 154(3):651–663. doi:https://doi.org/10.1016/j.cell.2013.06.037CrossRefPubMed

33.

Margadant C (2020) Positive and negative feedback mechanisms controlling tip/stalk cell identity during sprouting angiogenesis. Angiogenesis 23(2):75–77. doi:https://doi.org/10.1007/s10456-020-09706-0CrossRefPubMed

34.

Ma Q, Reiter RJ, Chen Y (2020) Role of melatonin in controlling angiogenesis under physiological and pathological conditions. Angiogenesis 23(2):91–104. doi:https://doi.org/10.1007/s10456-019-09689-7CrossRefPubMed

35.

Lustgarten Guahmich N, Farber G, Shafiei S, McNally D, Redmond D, Kallinos E, Stuhlmann H, Dufort D, James D, Blobel CP (2020) Endothelial deletion of ADAM10, a key regulator of Notch signaling, causes impaired decidualization and reduced fertility in female mice. Angiogenesis 23(3):443–458. doi:https://doi.org/10.1007/s10456-020-09723-zCrossRefPubMed

36.

Hwang MH, Kim S (2014) Type 2 diabetes: endothelial dysfunction and exercise. J Exerc Nutr Biochem 18(3):239–247. https://doi.org/10.5717/jenb.2014.18.3.239CrossRef

37.

Latacz E, Caspani E, Barnhill R, Lugassy C, Verhoef C, Grünhagen D, Van Laere S, Fernández Moro C, Gerling M, Dirix M, Dirix LY, Vermeulen PB (2020) Pathological features of vessel co-option versus sprouting angiogenesis. Angiogenesis 23(1):43–54. doi:https://doi.org/10.1007/s10456-019-09690-0CrossRefPubMed

38.

Sabbatinelli J, Prattichizzo F, Olivieri F, Procopio AD, Rippo MR, Giuliani A (2019) Where metabolism meets senescence: focus on endothelial cells. Front Physiol 10:1523. https://doi.org/10.3389/fphys.2019.01523CrossRefPubMedPubMedCentral

39.

Dagher Z, Ruderman N, Tornheim K, Ido Y (2001) Acute regulation of fatty acid oxidation and amp-activated protein kinase in human umbilical vein endothelial cells. Circul Res 88(12):1276–1282. doi:https://doi.org/10.1161/hh1201.092998CrossRef

40.

Leopold JA, Cap A, Scribner AW, Stanton RC, Loscalzo J (2001) Glucose-6-phosphate dehydrogenase deficiency promotes endothelial oxidant stress and decreases endothelial nitric oxide bioavailability. Faseb j 15(10):1771–1773. doi:https://doi.org/10.1096/fj.00-0893fjeCrossRefPubMed

41.

Merchan JR, Kovács K, Railsback JW, Kurtoglu M, Jing Y, Piña Y, Gao N, Murray TG, Lehrman MA, Lampidis TJ (2010) Antiangiogenic activity of 2-deoxy-D-glucose. PLoS ONE 5(10):e13699. doi:https://doi.org/10.1371/journal.pone.0013699CrossRefPubMedPubMedCentral

42.

Kuczynski EA, Reynolds AR (2020) Vessel co-option and resistance to anti-angiogenic therapy. Angiogenesis 23(1):55–74. doi:https://doi.org/10.1007/s10456-019-09698-6CrossRefPubMed

43.

McElwain CJ, Tuboly E, McCarthy FP, McCarthy CM (2020) Mechanisms of endothelial dysfunction in pre-eclampsia and gestational diabetes mellitus: windows into future cardiometabolic health? Front Endocrinol 11:655. https://doi.org/10.3389/fendo.2020.00655CrossRef

44.

Knapp M, Tu X, Wu R (2019) Vascular endothelial dysfunction, a major mediator in diabetic cardiomyopathy. Acta Pharmacol Sin 40(1):1–8. doi:https://doi.org/10.1038/s41401-018-0042-6CrossRefPubMed

45.

Tang X, Luo YX, Chen HZ, Liu DP (2014) Mitochondria, endothelial cell function, and vascular diseases. Front Physiol 5:175. doi:https://doi.org/10.3389/fphys.2014.00175CrossRefPubMedPubMedCentral

46.

Drummond GR, Sobey CG (2014) Endothelial NADPH oxidases: which NOX to target in vascular disease? Trends in endocrinology and metabolism. TEM 25(9):452–463. doi:https://doi.org/10.1016/j.tem.2014.06.012CrossRefPubMed

47.

Koh JH, Johnson ML, Dasari S, LeBrasseur NK, Vuckovic I, Henderson GC, Cooper SA, Manjunatha S, Ruegsegger GN, Shulman GI, Lanza IR, Nair KS (2019) TFAM Enhances Fat Oxidation and Attenuates High-Fat Diet-Induced Insulin Resistance in Skeletal Muscle. Diabetes 68(8):1552–1564. doi:https://doi.org/10.2337/db19-0088CrossRefPubMedPubMedCentral

48.

D’Souza K, Nzirorera C, Kienesberger PC (2016) Lipid metabolism and signaling in cardiac lipotoxicity. Biochim Biophys Acta 1861(10):1513–1524. doi:https://doi.org/10.1016/j.bbalip.2016.02.016CrossRefPubMed

49.

Ko VH, Yu LJ, Dao DT, Li X, Secor JD, Anez-Bustillos L, Cho BS, Pan A, Mitchell PD, Kishikawa H, Puder M (2020) Roxadustat (FG-4592) accelerates pulmonary growth, development, and function in a compensatory lung growth model. Angiogenesis. doi:https://doi.org/10.1007/s10456-020-09735-9CrossRefPubMed

50.

Pangare M, Makino A (2012) Mitochondrial function in vascular endothelial cell in diabetes. J Smooth Muscle Res 48(1):1–26. https://doi.org/10.1540/jsmr.48.1CrossRefPubMed

51.

Shenouda SM, Widlansky ME, Chen K, Xu G, Holbrook M, Tabit CE, Hamburg NM, Frame AA, Caiano TL, Kluge MA, Duess MA, Levit A, Kim B, Hartman ML, Joseph L, Shirihai OS, Vita JA (2011) Altered mitochondrial dynamics contributes to endothelial dysfunction in diabetes mellitus. Circulation 124(4):444–453. doi:https://doi.org/10.1161/circulationaha.110.014506CrossRefPubMedPubMedCentral

52.

Du XL, Edelstein D, Rossetti L, Fantus IG, Goldberg H, Ziyadeh F, Wu J, Brownlee M (2000) Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation. Proc Natl Acad Sci USA 97(22):12222–12226. doi:https://doi.org/10.1073/pnas.97.22.12222CrossRefPubMedPubMedCentral

53.

Du X, Matsumura T, Edelstein D, Rossetti L, Zsengellér Z, Szabó C, Brownlee M (2003) Inhibition of GAPDH activity by poly(ADP-ribose) polymerase activates three major pathways of hyperglycemic damage in endothelial cells. J Clin Investig 112(7):1049–1057. doi:https://doi.org/10.1172/jci18127CrossRefPubMedPubMedCentral

54.

Devalaraja-Narashimha K, Padanilam BJ (2009) PARP-1 inhibits glycolysis in ischemic kidneys. J Am Soc Nephrol 20(1):95–103. https://doi.org/10.1681/asn.2008030325CrossRefPubMedPubMedCentral

55.

Jiang L, Li N (2020) B-cell non-Hodgkin lymphoma: importance of angiogenesis and antiangiogenic therapy. Angiogenesis. doi:https://doi.org/10.1007/s10456-020-09729-7CrossRefPubMed

56.

Ceriello A, Ihnat MA, Thorpe JE (2009) Clinical review 2: The “metabolic memory”: is more than just tight glucose control necessary to prevent diabetic complications? J Clin Endocrinol Metab 94(2):410–415. doi:https://doi.org/10.1210/jc.2008-1824CrossRefPubMed

57.

Wautier JL, Schmidt AM (2004) Protein glycation: a firm link to endothelial cell dysfunction. Circul Res 95(3):233–238. doi:https://doi.org/10.1161/01.Res.0000137876.28454.64CrossRef

58.

Federici M, Menghini R, Mauriello A, Hribal ML, Ferrelli F, Lauro D, Sbraccia P, Spagnoli LG, Sesti G, Lauro R (2002) Insulin-dependent activation of endothelial nitric oxide synthase is impaired by O-linked glycosylation modification of signaling proteins in human coronary endothelial cells. Circulation 106(4):466–472. doi:https://doi.org/10.1161/01.cir.0000023043.02648.51CrossRefPubMed

59.

Das Evcimen N, King GL (2007) The role of protein kinase C activation and the vascular complications of diabetes. Pharmacol Res 55(6):498–510. doi:https://doi.org/10.1016/j.phrs.2007.04.016CrossRefPubMed

60.

Chang T, Wang R, Wu L (2005) Methylglyoxal-induced nitric oxide and peroxynitrite production in vascular smooth muscle cells. Free Radic Biol Med 38(2):286–293. doi:https://doi.org/10.1016/j.freeradbiomed.2004.10.034CrossRefPubMed

61.

Sena CM, Matafome P, Crisóstomo J, Rodrigues L, Fernandes R, Pereira P, Seiça RM (2012) Methylglyoxal promotes oxidative stress and endothelial dysfunction. Pharmacol Res 65(5):497–506. doi:https://doi.org/10.1016/j.phrs.2012.03.004CrossRefPubMed

62.

Islam MT (2020) Angiostatic effects of ascorbic acid: current status and future perspectives. Angiogenesis 23(3):275–277. doi:https://doi.org/10.1007/s10456-020-09719-9CrossRefPubMed

63.

Matafome P, Sena C, Seiça R (2013) Methylglyoxal, obesity, and diabetes. Endocrine 43(3):472–484. doi:https://doi.org/10.1007/s12020-012-9795-8CrossRefPubMed

64.

Pan M, Han Y, Basu A, Dai A, Si R, Willson C, Balistrieri A, Scott BT, Makino A (2018) Overexpression of hexokinase 2 reduces mitochondrial calcium overload in coronary endothelial cells of type 2 diabetic mice. Am J Physiol Cell Physiol 314(6):C732–c740. doi:https://doi.org/10.1152/ajpcell.00350.2017CrossRefPubMedPubMedCentral

65.

Alvarado-Vásquez N, Zapata E, Alcázar-Leyva S, Massó F, Montaño LF (2007) Reduced NO synthesis and eNOS mRNA expression in endothelial cells from newborns with a strong family history of type 2 diabetes. Diabetes/Metab Res Rev 23(7):559–566. https://doi.org/10.1002/dmrr.743CrossRef

66.

Moruzzi N, Del Sole M, Fato R, Gerdes JM, Berggren PO, Bergamini C, Brismar K (2014) Short and prolonged exposure to hyperglycaemia in human fibroblasts and endothelial cells: metabolic and osmotic effects. Int J Biochem Cell Biol 53:66–76. doi:https://doi.org/10.1016/j.biocel.2014.04.026CrossRefPubMed

67.

Kim EH, Koh EH, Park JY, Lee KU (2010) Adenine nucleotide translocator as a regulator of mitochondrial function: implication in the pathogenesis of metabolic syndrome. Korean Diabetes J 34(3):146–153. https://doi.org/10.4093/kdj.2010.34.3.146CrossRefPubMedPubMedCentral

68.

Gerő D, Torregrossa R, Perry A, Waters A, Le-Trionnaire S, Whatmore JL, Wood M, Whiteman M (2016) The novel mitochondria-targeted hydrogen sulfide (H(2)S) donors AP123 and AP39 protect against hyperglycemic injury in microvascular endothelial cells in vitro. Pharmacol Res 113(Pt A):186–198. doi:https://doi.org/10.1016/j.phrs.2016.08.019CrossRefPubMedPubMedCentral

69.

Broniarek I, Koziel A, Jarmuszkiewicz W (2016) The effect of chronic exposure to high palmitic acid concentrations on the aerobic metabolism of human endothelial EA.hy926 cells. Pflug Arch 468(9):1541–1554. https://doi.org/10.1007/s00424-016-1856-zCrossRef

70.

Shah GN, Morofuji Y, Banks WA, Price TO (2013) High glucose-induced mitochondrial respiration and reactive oxygen species in mouse cerebral pericytes is reversed by pharmacological inhibition of mitochondrial carbonic anhydrases: Implications for cerebral microvascular disease in diabetes. Biochem Biophys Res Commun 440(2):354–358. doi:https://doi.org/10.1016/j.bbrc.2013.09.086CrossRefPubMed

71.

Shah GN, Price TO, Banks WA, Morofuji Y, Kovac A, Ercal N, Sorenson CM, Shin ES, Sheibani N (2013) Pharmacological inhibition of mitochondrial carbonic anhydrases protects mouse cerebral pericytes from high glucose-induced oxidative stress and apoptosis. J Pharmacol Exp Ther 344(3):637–645. doi:https://doi.org/10.1124/jpet.112.201400CrossRefPubMedPubMedCentral

72.

Chan DC (2020) Mitochondrial Dynamics and Its Involvement in Disease. Annu Rev Pathol 15:235–259. doi:https://doi.org/10.1146/annurev-pathmechdis-012419-032711CrossRefPubMed

73.

Giacomello M, Pyakurel A, Glytsou C, Scorrano L (2020) The cell biology of mitochondrial membrane dynamics. Nat Rev Mol Cell Biol 21(4):204–224. doi:https://doi.org/10.1038/s41580-020-0210-7CrossRefPubMed

74.

Xian H, Liou YC (2021) Functions of outer mitochondrial membrane proteins: mediating the crosstalk between mitochondrial dynamics and mitophagy. Cell Death Differ 28(3):827–842. doi:https://doi.org/10.1038/s41418-020-00657-zCrossRefPubMed

75.

Whitley BN, Engelhart EA, Hoppins S (2019) Mitochondrial dynamics and their potential as a therapeutic target. Mitochondrion 49:269–283. doi:https://doi.org/10.1016/j.mito.2019.06.002CrossRefPubMedPubMedCentral

76.

Vásquez-Trincado C, García-Carvajal I, Pennanen C, Parra V, Hill JA, Rothermel BA, Lavandero S (2016) Mitochondrial dynamics, mitophagy and cardiovascular disease. J Physiol 594(3):509–525. doi:https://doi.org/10.1113/jp271301CrossRefPubMedPubMedCentral

77.

Mishra P, Chan DC (2016) Metabolic regulation of mitochondrial dynamics. J Cell Biol 212(4):379–387. doi:https://doi.org/10.1083/jcb.201511036CrossRefPubMedPubMedCentral

78.

Zhou H, Hu S, Jin Q, Shi C, Zhang Y, Zhu P, Ma Q, Tian F, Chen Y (2017) Mff-dependent mitochondrial fission contributes to the pathogenesis of cardiac microvasculature ischemia/reperfusion injury via induction of mROS-mediated cardiolipin oxidation and HK2/VDAC1 disassociation-involved mPTP opening. J Am Heart Assoc. https://doi.org/10.1161/JAHA.116.005328CrossRefPubMedPubMedCentral

79.

Jin Q, Li R, Hu N, Xin T, Zhu P, Hu S, Ma S, Zhu H, Ren J, Zhou H (2018) DUSP1 alleviates cardiac ischemia/reperfusion injury by suppressing the Mff-required mitochondrial fission and Bnip3-related mitophagy via the JNK pathways. Redox Biol 14:576–587. doi:https://doi.org/10.1016/j.redox.2017.11.004CrossRefPubMed

80.

Ikeda Y, Shirakabe A, Maejima Y, Zhai P, Sciarretta S, Toli J, Nomura M, Mihara K, Egashira K, Ohishi M, Abdellatif M, Sadoshima J (2015) Endogenous Drp1 mediates mitochondrial autophagy and protects the heart against energy stress. Circ Res 116(2):264–278. doi:https://doi.org/10.1161/circresaha.116.303356CrossRefPubMed

81.

Song M, Franco A, Fleischer JA, Zhang L, Dorn GW II (2017) Abrogating mitochondrial dynamics in mouse hearts accelerates mitochondrial senescence. Cell Metab 26(6):872-883e875. https://doi.org/10.1016/j.cmet.2017.09.023CrossRefPubMedPubMedCentral

82.

Papanicolaou KN, Ngoh GA, Dabkowski ER, O’Connell KA, Ribeiro RF Jr, Stanley WC, Walsh K (2012) Cardiomyocyte deletion of mitofusin-1 leads to mitochondrial fragmentation and improves tolerance to ROS-induced mitochondrial dysfunction and cell death. Am J Physiol Heart Circ Physiol 302(1):H167–179. doi:https://doi.org/10.1152/ajpheart.00833.2011CrossRefPubMed

83.

Papanicolaou KN, Khairallah RJ, Ngoh GA, Chikando A, Luptak I, O’Shea KM, Riley DD, Lugus JJ, Colucci WS, Lederer WJ, Stanley WC, Walsh K (2011) Mitofusin-2 maintains mitochondrial structure and contributes to stress-induced permeability transition in cardiac myocytes. Mol Cell Biol 31(6):1309–1328. doi:https://doi.org/10.1128/mcb.00911-10CrossRefPubMedPubMedCentral

84.

Hall AR, Burke N, Dongworth RK, Kalkhoran SB, Dyson A, Vicencio JM, Dorn GW, Yellon II, Hausenloy DM DJ (2016) Hearts deficient in both Mfn1 and Mfn2 are protected against acute myocardial infarction. Cell Death Dis 7(5):e2238. doi:https://doi.org/10.1038/cddis.2016.139CrossRefPubMedPubMedCentral

85.

Cipolat S, Martins de Brito O, Dal Zilio B, Scorrano L (2004) OPA1 requires mitofusin 1 to promote mitochondrial fusion. Proc Natl Acad Sci USA 101(45):15927–15932. doi:https://doi.org/10.1073/pnas.0407043101CrossRefPubMedPubMedCentral

86.

Varanita T, Soriano ME, Romanello V, Zaglia T, Quintana-Cabrera R, Semenzato M, Menabò R, Costa V, Civiletto G, Pesce P, Viscomi C, Zeviani M, Di Lisa F, Mongillo M, Sandri M, Scorrano L (2015) The OPA1-dependent mitochondrial cristae remodeling pathway controls atrophic, apoptotic, and ischemic tissue damage. Cell Metab 21(6):834–844. doi:https://doi.org/10.1016/j.cmet.2015.05.007CrossRefPubMedPubMedCentral

87.

Civiletto G, Varanita T, Cerutti R, Gorletta T, Barbaro S, Marchet S, Lamperti C, Viscomi C, Scorrano L, Zeviani M (2015) Opa1 overexpression ameliorates the phenotype of two mitochondrial disease mouse models. Cell Metab 21(6):845–854. doi:https://doi.org/10.1016/j.cmet.2015.04.016CrossRefPubMedPubMedCentral

88.

Bravo-San Pedro JM, Kroemer G, Galluzzi L (2017) Autophagy and Mitophagy in Cardiovascular Disease. Circ Res 120(11):1812–1824. doi:https://doi.org/10.1161/circresaha.117.311082CrossRefPubMed

89.

Hoshino A, Mita Y, Okawa Y, Ariyoshi M, Iwai-Kanai E, Ueyama T, Ikeda K, Ogata T, Matoba S (2013) Cytosolic p53 inhibits Parkin-mediated mitophagy and promotes mitochondrial dysfunction in the mouse heart. Nat Commun 4:2308. doi:https://doi.org/10.1038/ncomms3308CrossRefPubMed

90.

Rana A, Rera M, Walker DW (2013) Parkin overexpression during aging reduces proteotoxicity, alters mitochondrial dynamics, and extends lifespan. Proc Natl Acad Sci U S A 110(21):8638–8643. doi:https://doi.org/10.1073/pnas.1216197110CrossRefPubMedPubMedCentral

91.

Billia F, Hauck L, Konecny F, Rao V, Shen J, Mak TW (2011) PTEN-inducible kinase 1 (PINK1)/Park6 is indispensable for normal heart function. Proc Natl Acad Sci U S A 108(23):9572–9577. doi:https://doi.org/10.1073/pnas.1106291108CrossRefPubMedPubMedCentral

92.

Siddall HK, Yellon DM, Ong SB, Mukherjee UA, Burke N, Hall AR, Angelova PR, Ludtmann MH, Deas E, Davidson SM, Mocanu MM, Hausenloy DJ (2013) Loss of PINK1 increases the heart’s vulnerability to ischemia-reperfusion injury. PLoS ONE 8(4):e62400. doi:https://doi.org/10.1371/journal.pone.0062400CrossRefPubMedPubMedCentral

93.

Diwan A, Krenz M, Syed FM, Wansapura J, Ren X, Koesters AG, Li H, Kirshenbaum LA, Hahn HS, Robbins J, Jones WK, Dorn GW (2007) Inhibition of ischemic cardiomyocyte apoptosis through targeted ablation of Bnip3 restrains postinfarction remodeling in mice. J Clin Invest 117(10):2825–2833. doi:https://doi.org/10.1172/jci32490CrossRefPubMedPubMedCentral

94.

Yussman MG, Toyokawa T, Odley A, Lynch RA, Wu G, Colbert MC, Aronow BJ, Lorenz JN, Dorn GW IInd (2002) Mitochondrial death protein Nix is induced in cardiac hypertrophy and triggers apoptotic cardiomyopathy. Nat Med 8(7):725–730. doi:https://doi.org/10.1038/nm719CrossRefPubMed

95.

Wu S, Lu Q, Wang Q, Ding Y, Ma Z, Mao X, Huang K, Xie Z, Zou MH (2017) Binding of FUN14 domain containing 1 with inositol 1,4,5-trisphosphate receptor in mitochondria-associated endoplasmic reticulum membranes maintains mitochondrial dynamics and function in hearts in vivo. Circulation 136(23):2248–2266. https://doi.org/10.1161/circulationaha.117.030235CrossRefPubMedPubMedCentral

96.

García-Quintans N, Sánchez-Ramos C, Prieto I, Tierrez A, Arza E, Alfranca A, Redondo JM, Monsalve M (2016) Oxidative stress induces loss of pericyte coverage and vascular instability in PGC-1α-deficient mice. Angiogenesis 19(2):217–228. doi:https://doi.org/10.1007/s10456-016-9502-0CrossRefPubMed

97.

Riehle C, Abel ED (2012) PGC-1 proteins and heart failure. Trends Cardiovasc Med 22(4):98–105. doi:https://doi.org/10.1016/j.tcm.2012.07.003CrossRefPubMedPubMedCentral

98.

Koshiba T, Detmer SA, Kaiser JT, Chen H, McCaffery JM, Chan DC (2004) Structural basis of mitochondrial tethering by mitofusin complexes. Science 305(5685):858–862. https://doi.org/10.1126/science.1099793CrossRefPubMed

99.

Chen H, Detmer SA, Ewald AJ, Griffin EE, Fraser SE, Chan DC (2003) Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. J Cell Biol 160(2):189–200. https://doi.org/10.1083/jcb.200211046CrossRefPubMedPubMedCentral

100.

Ishihara N, Fujita Y, Oka T, Mihara K (2006) Regulation of mitochondrial morphology through proteolytic cleavage of OPA1. Embo j 25(13):2966–2977. doi:https://doi.org/10.1038/sj.emboj.7601184CrossRefPubMedPubMedCentral

101.

Anand R, Wai T, Baker MJ, Kladt N, Schauss AC, Rugarli E, Langer T (2014) The i-AAA protease YME1L and OMA1 cleave OPA1 to balance mitochondrial fusion and fission. J Cell Biol 204(6):919–929. doi:https://doi.org/10.1083/jcb.201308006CrossRefPubMedPubMedCentral

102.

Duvezin-Caubet S, Jagasia R, Wagener J, Hofmann S, Trifunovic A, Hansson A, Chomyn A, Bauer MF, Attardi G, Larsson NG, Neupert W, Reichert AS (2006) Proteolytic processing of OPA1 links mitochondrial dysfunction to alterations in mitochondrial morphology. J Biol Chem 281(49):37972–37979. doi:https://doi.org/10.1074/jbc.M606059200CrossRefPubMed

103.

Bakuy V, Unal O, Gursoy M, Kunt A, Ozisik K, Sargon M, Emir M, Sener E (2014) Electron microscopic evaluation of internal thoracic artery endothelial morphology in diabetic coronary bypass patients. Ann Thorac Surg 97(3):851–857. doi:https://doi.org/10.1016/j.athoracsur.2013.09.102CrossRefPubMed

104.

Wang W, Wang Y, Long J, Wang J, Haudek SB, Overbeek P, Chang BH, Schumacker PT, Danesh FR (2012) Mitochondrial fission triggered by hyperglycemia is mediated by ROCK1 activation in podocytes and endothelial cells. Cell Metabol 15(2):186–200. doi:https://doi.org/10.1016/j.cmet.2012.01.009CrossRef

105.

Di Tomo P, Alessio N, Falone S, Pietrangelo L, Lanuti P, Cordone V, Santini SJ, Di Pietrantonio N, Marchisio M, Protasi F, Di Pietro N, Formoso G, Amicarelli F, Galderisi U, Pandolfi A (2021) Endothelial cells from umbilical cord of women affected by gestational diabetes: A suitable in vitro model to study mechanisms of early vascular senescence in diabetes. Faseb j 35(6):e21662. doi:https://doi.org/10.1096/fj.202002072RRCrossRefPubMed

106.

Xing H, Zhang Z, Shi G, He Y, Song Y, Liu Y, Harrington EO, Sellke FW, Feng J (2021) Chronic Inhibition of mROS Protects Against Coronary Endothelial Dysfunction in Mice With Diabetes. Front Cell Dev Biol 9:643810. doi:https://doi.org/10.3389/fcell.2021.643810CrossRefPubMedPubMedCentral

107.

Makino A, Scott BT, Dillmann WH (2010) Mitochondrial fragmentation and superoxide anion production in coronary endothelial cells from a mouse model of type 1 diabetes. Diabetologia 53(8):1783–1794. doi:https://doi.org/10.1007/s00125-010-1770-4CrossRefPubMedPubMedCentral

108.

Durand MJ, Ait-Aissa K, Levchenko V, Staruschenko A, Gutterman DD, Beyer AM (2019) Visualization and quantification of mitochondrial structure in the endothelium of intact arteries. Cardiovascular Res 115(10):1546–1556. doi:https://doi.org/10.1093/cvr/cvy294CrossRef

109.

García-Martínez E, Redondo A, Piulats JM, Rodríguez A, Casado A (2020) Are antiangiogenics a good ‘partner’ for immunotherapy in ovarian cancer? Angiogenesis. https://doi.org/10.1007/s10456-020-09734-wCrossRefPubMedPubMedCentral

110.

García-Gómez P, Valiente M (2020) Vascular co-option in brain metastasis. Angiogenesis 23(1):3–8. doi:https://doi.org/10.1007/s10456-019-09693-xCrossRefPubMed

111.

Fukada K, Kajiya K (2020) Age-related structural alterations of skeletal muscles and associated capillaries. Angiogenesis 23(2):79–82. doi:https://doi.org/10.1007/s10456-020-09705-1CrossRefPubMed

112.

Iannantuoni F, Abad-Jiménez AMdM, Canet Z, Díaz-Pozo F, López-Domènech P, Morillas S, Rocha C, Víctor MVM (2020) Mitochondrial alterations and enhanced human leukocyte/endothelial cell interactions in type 1 diabetes. J Clin Med. https://doi.org/10.3390/jcm9072155CrossRefPubMedPubMedCentral

113.

Chen W, Xiang H, Chen R, Yang J, Yang X, Zhou J, Liu H, Zhao S, Xiao J, Chen P, Chen AF, Chen S, Lu H (2019) S1PR2 antagonist ameliorate high glucose-induced fission and dysfunction of mitochondria in HRGECs via regulating ROCK1. BMC Nephrol 20(1):135. doi:https://doi.org/10.1186/s12882-019-1323-0CrossRefPubMedPubMedCentral

114.

Lee HZ, Yeh FT, Wu CH (2004) The effect of elevated extracellular glucose on adherens junction proteins in cultured rat heart endothelial cells. Life Sci 74(17):2085–2096. doi:https://doi.org/10.1016/j.lfs.2003.06.046CrossRefPubMed

115.

Zhou H, Wang S, Zhu P, Hu S, Chen Y, Ren J (2018) Empagliflozin rescues diabetic myocardial microvascular injury via AMPK-mediated inhibition of mitochondrial fission. Redox Biol 15:335–346. doi:https://doi.org/10.1016/j.redox.2017.12.019CrossRefPubMed

116.

Kim D, Sesaki H, Roy S (2021) Reduced levels of Drp1 protect against development of retinal vascular lesions in diabetic retinopathy. Cells. https://doi.org/10.3390/cells10061379CrossRefPubMedPubMedCentral

117.

Kim D, Roy S (2020) Effects of diabetes on mitochondrial morphology and its implications in diabetic retinopathy. Investig Ophthalmol Vis Sci 61(10):10. https://doi.org/10.1167/iovs.61.10.10CrossRef

118.

Kowluru RA, Mohammad G (2020) Epigenetics and Mitochondrial Stability in the Metabolic Memory Phenomenon Associated with Continued Progression of Diabetic Retinopathy. Sci Rep 10(1):6655. doi:https://doi.org/10.1038/s41598-020-63527-1CrossRefPubMedPubMedCentral

119.

Duraisamy AJ, Mohammad G, Kowluru RA (2019) Mitochondrial fusion and maintenance of mitochondrial homeostasis in diabetic retinopathy. Biochim Biophys Acta 1865(6):1617–1626. https://doi.org/10.1016/j.bbadis.2019.03.013CrossRef

120.

Shi Y, Fan S, Wang D, Huyan T, Chen J, Chen J, Su J, Li X, Wang Z, Xie S, Yun C, Li X, Tie L (2018) FOXO1 inhibition potentiates endothelial angiogenic functions in diabetes via suppression of ROCK1/Drp1-mediated mitochondrial fission. Biochim Biophys Acta 1864(7):2481–2494. https://doi.org/10.1016/j.bbadis.2018.04.005CrossRef

121.

Kim YM, Youn SW, Sudhahar V, Das A, Chandhri R, Cuervo Grajal H, Kweon J, Leanhart S, He L, Toth PT, Kitajewski J, Rehman J, Yoon Y, Cho J, Fukai T, Ushio-Fukai M (2018) Redox Regulation of Mitochondrial Fission Protein Drp1 by Protein Disulfide Isomerase Limits Endothelial Senescence. Cell Rep 23(12):3565–3578. doi:https://doi.org/10.1016/j.celrep.2018.05.054CrossRefPubMedPubMedCentral

122.

Lemasters JJ (2014) Variants of mitochondrial autophagy: Types 1 and 2 mitophagy and micromitophagy (Type 3). Redox Biol 2:749–754. doi:https://doi.org/10.1016/j.redox.2014.06.004CrossRefPubMedPubMedCentral

123.

Czaja MJ, Ding WX, Donohue TM Jr, Friedman SL, Kim JS, Komatsu M, Lemasters JJ, Lemoine A, Lin JD, Ou JH, Perlmutter DH, Randall G, Ray RB, Tsung A, Yin XM (2013) Functions of autophagy in normal and diseased liver. Autophagy 9(8):1131–1158. doi:https://doi.org/10.4161/auto.25063CrossRefPubMedPubMedCentral

124.

Lemasters JJ, Zhong Z (2018) Mitophagy in hepatocytes: Types, initiators and role in adaptive ethanol metabolism☆. Liver Res 2(3):125–132. doi:https://doi.org/10.1016/j.livres.2018.09.005CrossRefPubMedPubMedCentral

125.

Kim I, Lemasters JJ (2011) Mitochondrial degradation by autophagy (mitophagy) in GFP-LC3 transgenic hepatocytes during nutrient deprivation. Am J Physiol Cell Physiol 300(2):C308–317. doi:https://doi.org/10.1152/ajpcell.00056.2010CrossRefPubMed

126.

Rodriguez-Enriquez S, Kim I, Currin RT, Lemasters JJ (2006) Tracker dyes to probe mitochondrial autophagy (mitophagy) in rat hepatocytes. Autophagy 2(1):39–46. doi:https://doi.org/10.4161/auto.2229CrossRefPubMed

127.

McLelland GL, Soubannier V, Chen CX, McBride HM, Fon EA (2014) Parkin and PINK1 function in a vesicular trafficking pathway regulating mitochondrial quality control. Embo j 33(4):282–295. doi:https://doi.org/10.1002/embj.201385902CrossRefPubMedPubMedCentral

128.

Cai Q, Jeong YY (2020) Mitophagy in Alzheimer’s disease and other age-related neurodegenerative diseases. Cells. https://doi.org/10.3390/cells9010150CrossRefPubMedPubMedCentral

129.

Fivenson EM, Lautrup S, Sun N, Scheibye-Knudsen M, Stevnsner T, Nilsen H, Bohr VA, Fang EF (2017) Mitophagy in neurodegeneration and aging. Neurochem Int 109:202–209. doi:https://doi.org/10.1016/j.neuint.2017.02.007CrossRefPubMedPubMedCentral

130.

Youle RJ, Narendra DP (2011) Mechanisms of mitophagy. Nat Rev Mol Cell Biol 12(1):9–14. doi:https://doi.org/10.1038/nrm3028CrossRefPubMedPubMedCentral

131.

Fritsch LE, Moore ME, Sarraf SA, Pickrell AM (2020) Ubiquitin and Receptor-Dependent Mitophagy Pathways and Their Implication in Neurodegeneration. J Mol Biol 432(8):2510–2524. doi:https://doi.org/10.1016/j.jmb.2019.10.015CrossRefPubMed

132.

Yamano K, Matsuda N, Tanaka K (2016) The ubiquitin signal and autophagy: an orchestrated dance leading to mitochondrial degradation. EMBO Rep 17(3):300–316. doi:https://doi.org/10.15252/embr.201541486CrossRefPubMedPubMedCentral

133.

Morales PE, Arias-Durán C, Ávalos-Guajardo Y, Aedo G, Verdejo HE, Parra V, Lavandero S (2020) Emerging role of mitophagy in cardiovascular physiology and pathology. Mol Aspects Med 71:100822. doi:https://doi.org/10.1016/j.mam.2019.09.006CrossRefPubMed

134.

Lazarou M, Sliter DA, Kane LA, Sarraf SA, Wang C, Burman JL, Sideris DP, Fogel AI, Youle RJ (2015) The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature 524(7565):309–314. doi:https://doi.org/10.1038/nature14893CrossRefPubMedPubMedCentral

135.

Liu L, Feng D, Chen G, Chen M, Zheng Q, Song P, Ma Q, Zhu C, Wang R, Qi W, Huang L, Xue P, Li B, Wang X, Jin H, Wang J, Yang F, Liu P, Zhu Y, Sui S, Chen Q (2012) Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells. Nat Cell Biol 14(2):177–185. doi:https://doi.org/10.1038/ncb2422CrossRefPubMed

136.

Zhou H, Zhu P, Wang J, Zhu H, Ren J, Chen Y (2018) Pathogenesis of cardiac ischemia reperfusion injury is associated with CK2alpha-disturbed mitochondrial homeostasis via suppression of FUNDC1-related mitophagy. Cell Death Differ 25(6):1080–1093. doi:https://doi.org/10.1038/s41418-018-0086-7CrossRefPubMedPubMedCentral

137.

Zhou H, Zhu P, Guo J, Hu N, Wang S, Li D, Hu S, Ren J, Cao F, Chen Y (2017) Ripk3 induces mitochondrial apoptosis via inhibition of FUNDC1 mitophagy in cardiac IR injury. Redox Biol 13:498–507. doi:https://doi.org/10.1016/j.redox.2017.07.007CrossRefPubMedPubMedCentral

138.

Zhou H, Wang J, Zhu P, Zhu H, Toan S, Hu S, Ren J, Chen Y (2018) NR4A1 aggravates the cardiac microvascular ischemia reperfusion injury through suppressing FUNDC1-mediated mitophagy and promoting Mff-required mitochondrial fission by CK2alpha. Basic Res Cardiol 113(4):23. doi:https://doi.org/10.1007/s00395-018-0682-1CrossRefPubMed

139.

Wang J, Zhu P, Li R, Ren J, Zhou H (2020) Fundc1-dependent mitophagy is obligatory to ischemic preconditioning-conferred renoprotection in ischemic AKI via suppression of Drp1-mediated mitochondrial fission. Redox Biol 30:101415. doi:https://doi.org/10.1016/j.redox.2019.101415CrossRefPubMed

140.

Gao A, Jiang J, Xie F, Chen L (2020) Bnip3 in mitophagy: Novel insights and potential therapeutic target for diseases of secondary mitochondrial dysfunction. Clin Chim Acta 506:72–83. doi:https://doi.org/10.1016/j.cca.2020.02.024CrossRefPubMed

141.

Schweers RL, Zhang J, Randall MS, Loyd MR, Li W, Dorsey FC, Kundu M, Opferman JT, Cleveland JL, Miller JL, Ney PA (2007) NIX is required for programmed mitochondrial clearance during reticulocyte maturation. Proc Natl Acad Sci USA 104(49):19500–19505. doi:https://doi.org/10.1073/pnas.0708818104CrossRefPubMedPubMedCentral

142.

Liu L, Sakakibara K, Chen Q, Okamoto K (2014) Receptor-mediated mitophagy in yeast and mammalian systems. Cell Res 24(7):787–795. doi:https://doi.org/10.1038/cr.2014.75CrossRefPubMedPubMedCentral

143.

Chen G, Cizeau J, Vande Velde C, Park JH, Bozek G, Bolton J, Shi L, Dubik D, Greenberg A (1999) Nix and Nip3 form a subfamily of pro-apoptotic mitochondrial proteins. J Biol Chem 274(1):7–10. doi:https://doi.org/10.1074/jbc.274.1.7CrossRefPubMed

144.

Xi J, Rong Y, Zhao Z, Huang Y, Wang P, Luan H, Xing Y, Li S, Liao J, Dai Y, Liang J, Wu F (2021) Scutellarin ameliorates high glucose-induced vascular endothelial cells injury by activating PINK1/Parkin-mediated mitophagy. J Ethnopharmacol 271:113855. doi:https://doi.org/10.1016/j.jep.2021.113855CrossRefPubMed

145.

Wu W, Xu H, Wang Z, Mao Y, Yuan L, Luo W, Cui Z, Cui T, Wang XL, Shen YH (2015) PINK1-Parkin-Mediated Mitophagy Protects Mitochondrial Integrity and Prevents Metabolic Stress-Induced Endothelial Injury. PLoS ONE 10(7):e0132499. doi:https://doi.org/10.1371/journal.pone.0132499CrossRefPubMedPubMedCentral

146.

Unterleuthner D, Neuhold P, Schwarz K, Janker L, Neuditschko B, Nivarthi H, Crncec I, Kramer N, Unger C, Hengstschläger M, Eferl R, Moriggl R, Sommergruber W, Gerner C, Dolznig H (2020) Cancer-associated fibroblast-derived WNT2 increases tumor angiogenesis in colon cancer. Angiogenesis 23(2):159–177. doi:https://doi.org/10.1007/s10456-019-09688-8CrossRefPubMed

147.

Umapathy A, Chamley LW, James JL (2020) Reconciling the distinct roles of angiogenic/anti-angiogenic factors in the placenta and maternal circulation of normal and pathological pregnancies. Angiogenesis 23(2):105–117. doi:https://doi.org/10.1007/s10456-019-09694-wCrossRefPubMed

148.

Tomita Y, Cakir B, Liu CH, Fu Z, Huang S, Cho SS, Britton WR, Sun Y, Puder M, Hellström A, Talukdar S, Smith LEH (2020) Free fatty acid receptor 4 activation protects against choroidal neovascularization in mice. Angiogenesis 23(3):385–394. doi:https://doi.org/10.1007/s10456-020-09717-xCrossRefPubMedPubMedCentral

149.

Tacconi C, He Y, Ducoli L, Detmar M (2020) Epigenetic regulation of the lineage specificity of primary human dermal lymphatic and blood vascular endothelial cells. Angiogenesis. doi:https://doi.org/10.1007/s10456-020-09743-9CrossRefPubMedPubMedCentral

150.

Szulcek R, Sanchez-Duffhues G, Rol N, Pan X, Tsonaka R, Dickhoff C, Yung LM, Manz XD, Kurakula K, Kiełbasa SM, Mei H, Timens W, Yu PB, Bogaard HJ, Goumans MJ (2020) Exacerbated inflammatory signaling underlies aberrant response to BMP9 in pulmonary arterial hypertension lung endothelial cells. Angiogenesis. doi:https://doi.org/10.1007/s10456-020-09741-xCrossRefPubMedPubMedCentral

151.

Szaraz P, Mander P, Gasner N, Librach M, Iqbal F, Librach C (2020) Glucose withdrawal induces Endothelin 1 release with significant angiogenic effect from first trimester (FTM), but not term human umbilical cord perivascular cells (HUCPVC). Angiogenesis 23(2):131–144. doi:https://doi.org/10.1007/s10456-019-09682-0CrossRefPubMed

152.

Smadja DM, Guerin CL, Chocron R, Yatim N, Boussier J, Gendron N, Khider L, Hadjadj J, Goudot G, Debuc B, Juvin P, Hauw-Berlemont C, Augy JL, Peron N, Messas E, Planquette B, Sanchez O, Charbit B, Gaussem P, Duffy D, Terrier B, Mirault T, Diehl JL (2020) Angiopoietin-2 as a marker of endothelial activation is a good predictor factor for intensive care unit admission of COVID-19 patients. Angiogenesis. https://doi.org/10.1007/s10456-020-09730-0CrossRefPubMedPubMedCentral

153.

Wang X, Zhang JQ, Xiu CK, Yang J, Fang JY, Lei Y (2020) Ginseng-Sanqi-Chuanxiong (GSC) extracts ameliorate diabetes-induced endothelial cell senescence through regulating mitophagy via the AMPK pathway. Oxid Med Cell Longev 2020:7151946. https://doi.org/10.1155/2020/7151946CrossRefPubMedPubMedCentral

154.

Jin H, Zhu Y, Li Y, Ding X, Ma W, Han X, Wang B (2019) BDNF-mediated mitophagy alleviates high-glucose-induced brain microvascular endothelial cell injury. Apoptosis 24(5–6):511–528. doi:https://doi.org/10.1007/s10495-019-01535-xCrossRefPubMed

155.

Yoshibayashi M, Kume S, Yasuda-Yamahara M, Yamahara K, Takeda N, Osawa N, Chin-Kanasaki M, Nakae Y, Yokoi H, Mukoyama M, Asanuma K, Maegawa H, Araki SI (2020) Protective role of podocyte autophagy against glomerular endothelial dysfunction in diabetes. Biochem Biophys Res Commun 525(2):319–325. doi:https://doi.org/10.1016/j.bbrc.2020.02.088CrossRefPubMed

156.

Vaeyens MM, Jorge-Peñas A, Barrasa-Fano J, Steuwe C, Heck T, Carmeliet P, Roeffaers M, Van Oosterwyck H (2020) Matrix deformations around angiogenic sprouts correlate to sprout dynamics and suggest pulling activity. Angiogenesis 23(3):315–324. doi:https://doi.org/10.1007/s10456-020-09708-yCrossRefPubMed

157.

Zhu W, Yuan Y, Liao G, Li L, Liu J, Chen Y, Zhang J, Cheng J, Lu Y (2018) Mesenchymal stem cells ameliorate hyperglycemia-induced endothelial injury through modulation of mitophagy. Cell Death Dis 9(8):837. doi:https://doi.org/10.1038/s41419-018-0861-xCrossRefPubMedPubMedCentral

158.

Hill JH, Chen Z, Xu H (2014) Selective propagation of functional mitochondrial DNA during oogenesis restricts the transmission of a deleterious mitochondrial variant. Nat Genet 46(4):389–392. doi:https://doi.org/10.1038/ng.2920CrossRefPubMedPubMedCentral

159.

Fournier P, Viallard C, Dejda A, Sapieha P, Larrivée B, Royal I (2020) The protein tyrosine phosphatase PTPRJ/DEP-1 contributes to the regulation of the Notch-signaling pathway and sprouting angiogenesis. Angiogenesis 23(2):145–157. doi:https://doi.org/10.1007/s10456-019-09683-zCrossRefPubMed

160.

Domingues A, Boisson-Vidal C, Marquet de Rouge P, Dizier B, Sadoine J, Mignon V, Vessières E, Henrion D, Escriou V, Bigey P, Chaussain C, Smadja DM, Nivet-Antoine V (2020) Targeting endothelial thioredoxin-interacting protein (TXNIP) protects from metabolic disorder-related impairment of vascular function and post-ischemic revascularisation. Angiogenesis 23(2):249–264. doi:https://doi.org/10.1007/s10456-019-09704-xCrossRefPubMed

161.

Dieterich LC, Tacconi C, Menzi F, Proulx ST, Kapaklikaya K, Hamada M, Takahashi S, Detmar M (2020) Lymphatic MAFB regulates vascular patterning during developmental and pathological lymphangiogenesis. Angiogenesis 23(3):411–423. doi:https://doi.org/10.1007/s10456-020-09721-1CrossRefPubMedPubMedCentral

162.

di Somma M, Vliora M, Grillo E, Castro B, Dakou E, Schaafsma W, Vanparijs J, Corsini M, Ravelli C, Sakellariou E, Mitola S (2020) Role of VEGFs in metabolic disorders. Angiogenesis 23(2):119–130. doi:https://doi.org/10.1007/s10456-019-09700-1CrossRefPubMed

163.

Depoix CL, Colson A, Hubinont C, Debieve F (2020) Impaired vascular endothelial growth factor expression and secretion during in vitro differentiation of human primary term cytotrophoblasts. Angiogenesis 23(2):221–230. doi:https://doi.org/10.1007/s10456-019-09702-zCrossRefPubMed

164.

Chen J, Lin FL, Leung JYK, Tu L, Wang JH, Chuang YF, Li F, Shen HH, Dusting GJ, Wong VHY, Lisowski L, Hewitt AW, Bui BV, Zhong J, Liu GS (2020) A drug-tunable Flt23k gene therapy for controlled intervention in retinal neovascularization. Angiogenesis. doi:https://doi.org/10.1007/s10456-020-09745-7CrossRefPubMedPubMedCentral

165.

Capasso TL, Li B, Volek HJ, Khalid W, Rochon ER, Anbalagan A, Herdman C, Yost HJ, Villanueva FS, Kim K, Roman BL (2020) BMP10-mediated ALK1 signaling is continuously required for vascular development and maintenance. Angiogenesis 23(2):203–220. doi:https://doi.org/10.1007/s10456-019-09701-0CrossRefPubMed

166.

Wallace DC (2008) Mitochondria as chi. Genetics 179(2):727–735. doi:https://doi.org/10.1534/genetics.104.91769CrossRefPubMedPubMedCentral

167.

Fox TD (2012) Mitochondrial protein synthesis, import, and assembly. Genetics 192(4):1203–1234. doi:https://doi.org/10.1534/genetics.112.141267CrossRefPubMedPubMedCentral

168.

Handschin C, Spiegelman BM (2006) Peroxisome proliferator-activated receptor gamma coactivator 1 coactivators, energy homeostasis, and metabolism. Endocr Rev 27(7):728–735. doi:https://doi.org/10.1210/er.2006-0037CrossRefPubMed

169.

Fan W, Evans R (2015) PPARs and ERRs: molecular mediators of mitochondrial metabolism. Curr Opin Cell Biol 33:49–54. doi:https://doi.org/10.1016/j.ceb.2014.11.002CrossRefPubMed

170.

Scarpulla RC (2011) Metabolic control of mitochondrial biogenesis through the PGC-1 family regulatory network. Biochim Biophys Acta 1813(7):1269–1278. doi:https://doi.org/10.1016/j.bbamcr.2010.09.019CrossRefPubMed

171.

Huo L, Scarpulla RC (2001) Mitochondrial DNA instability and peri-implantation lethality associated with targeted disruption of nuclear respiratory factor 1 in mice. Mol Cell Biol 21(2):644–654. doi:https://doi.org/10.1128/MCB.21.2.644-654.2001CrossRefPubMedPubMedCentral

172.

Ristevski S, O’Leary DA, Thornell AP, Owen MJ, Kola I, Hertzog PJ (2004) The ETS transcription factor GABPalpha is essential for early embryogenesis. Mol Cell Biol 24(13):5844–5849. doi:https://doi.org/10.1128/MCB.24.13.5844-5849.2004CrossRefPubMedPubMedCentral

173.

Aoyama T, Peters JM, Iritani N, Nakajima T, Furihata K, Hashimoto T, Gonzalez FJ (1998) Altered constitutive expression of fatty acid-metabolizing enzymes in mice lacking the peroxisome proliferator-activated receptor alpha (PPARalpha). J Biol Chem 273(10):5678–5684. doi:https://doi.org/10.1074/jbc.273.10.5678CrossRefPubMed

174.

Leone TC, Weinheimer CJ, Kelly DP (1999) A critical role for the peroxisome proliferator-activated receptor alpha (PPARalpha) in the cellular fasting response: the PPARalpha-null mouse as a model of fatty acid oxidation disorders. Proc Natl Acad Sci U S A 96(13):7473–7478. doi:https://doi.org/10.1073/pnas.96.13.7473CrossRefPubMedPubMedCentral

175.

Finck BN, Lehman JJ, Leone TC, Welch MJ, Bennett MJ, Kovacs A, Han X, Gross RW, Kozak R, Lopaschuk GD, Kelly DP (2002) The cardiac phenotype induced by PPARalpha overexpression mimics that caused by diabetes mellitus. J Clin Invest 109(1):121–130. doi:https://doi.org/10.1172/JCI14080CrossRefPubMedPubMedCentral

176.

Wang P, Liu J, Li Y, Wu S, Luo J, Yang H, Subbiah R, Chatham J, Zhelyabovska O, Yang Q (2010) Peroxisome proliferator-activated receptor {delta} is an essential transcriptional regulator for mitochondrial protection and biogenesis in adult heart. Circ Res 106(5):911–919. doi:https://doi.org/10.1161/CIRCRESAHA.109.206185CrossRefPubMedPubMedCentral

177.

Burkart EM, Sambandam N, Han X, Gross RW, Courtois M, Gierasch CM, Shoghi K, Welch MJ, Kelly DP (2007) Nuclear receptors PPARbeta/delta and PPARalpha direct distinct metabolic regulatory programs in the mouse heart. J Clin Invest 117(12):3930–3939. doi:https://doi.org/10.1172/JCI32578CrossRefPubMedPubMedCentral

178.

Duan SZ, Ivashchenko CY, Russell MW, Milstone DS, Mortensen RM (2005) Cardiomyocyte-specific knockout and agonist of peroxisome proliferator-activated receptor-gamma both induce cardiac hypertrophy in mice. Circ Res 97(4):372–379. doi:https://doi.org/10.1161/01.RES.0000179226.34112.6dCrossRefPubMed

179.

Son NH, Park TS, Yamashita H, Yokoyama M, Huggins LA, Okajima K, Homma S, Szabolcs MJ, Huang LS, Goldberg IJ (2007) Cardiomyocyte expression of PPARgamma leads to cardiac dysfunction in mice. J Clin Invest 117(10):2791–2801. doi:https://doi.org/10.1172/JCI30335CrossRefPubMedPubMedCentral

180.

Huss JM, Imahashi K, Dufour CR, Weinheimer CJ, Courtois M, Kovacs A, Giguere V, Murphy E, Kelly DP (2007) The nuclear receptor ERRalpha is required for the bioenergetic and functional adaptation to cardiac pressure overload. Cell Metab 6(1):25–37. doi:https://doi.org/10.1016/j.cmet.2007.06.005CrossRefPubMed

181.

Alaynick WA, Kondo RP, Xie W, He W, Dufour CR, Downes M, Jonker JW, Giles W, Naviaux RK, Giguere V, Evans RM (2007) ERRgamma directs and maintains the transition to oxidative metabolism in the postnatal heart. Cell Metab 6(1):13–24. doi:https://doi.org/10.1016/j.cmet.2007.06.007CrossRefPubMed

182.

Narkar VA, Fan W, Downes M, Yu RT, Jonker JW, Alaynick WA, Banayo E, Karunasiri MS, Lorca S, Evans RM (2011) Exercise and PGC-1alpha-independent synchronization of type I muscle metabolism and vasculature by ERRgamma. Cell Metab 13(3):283–293. doi:https://doi.org/10.1016/j.cmet.2011.01.019CrossRefPubMedPubMedCentral

183.

Blattler SM, Verdeguer F, Liesa M, Cunningham JT, Vogel RO, Chim H, Liu H, Romanino K, Shirihai OS, Vazquez F, Ruegg MA, Shi Y, Puigserver P (2012) Defective mitochondrial morphology and bioenergetic function in mice lacking the transcription factor Yin Yang 1 in skeletal muscle. Mol Cell Biol 32(16):3333–3346. doi:https://doi.org/10.1128/MCB.00337-12CrossRefPubMedPubMedCentral

184.

Ahuja P, Zhao P, Angelis E, Ruan H, Korge P, Olson A, Wang Y, Jin ES, Jeffrey FM, Portman M, Maclellan WR (2010) Myc controls transcriptional regulation of cardiac metabolism and mitochondrial biogenesis in response to pathological stress in mice. J Clin Invest 120(5):1494–1505. doi:https://doi.org/10.1172/JCI38331CrossRefPubMedPubMedCentral

185.

Martin OJ, Lai L, Soundarapandian MM, Leone TC, Zorzano A, Keller MP, Attie AD, Muoio DM, Kelly DP (2014) A role for peroxisome proliferator-activated receptor gamma coactivator-1 in the control of mitochondrial dynamics during postnatal cardiac growth. Circ Res 114(4):626–636. doi:https://doi.org/10.1161/CIRCRESAHA.114.302562CrossRefPubMed

186.

Lehman JJ, Barger PM, Kovacs A, Saffitz JE, Medeiros DM, Kelly DP (2000) Peroxisome proliferator-activated receptor gamma coactivator-1 promotes cardiac mitochondrial biogenesis. J Clin Invest 106(7):847–856. doi:https://doi.org/10.1172/JCI10268CrossRefPubMedPubMedCentral

187.

Arany Z, Novikov M, Chin S, Ma Y, Rosenzweig A, Spiegelman BM (2006) Transverse aortic constriction leads to accelerated heart failure in mice lacking PPAR-gamma coactivator 1alpha. Proc Natl Acad Sci U S A 103(26):10086–10091. doi:https://doi.org/10.1073/pnas.0603615103CrossRefPubMedPubMedCentral

188.

Chen W, Zhang X, Birsoy K, Roeder RG (2010) A muscle-specific knockout implicates nuclear receptor coactivator MED1 in the regulation of glucose and energy metabolism. Proc Natl Acad Sci U S A 107(22):10196–10201. doi:https://doi.org/10.1073/pnas.1005626107CrossRefPubMedPubMedCentral

189.

Neupert W, Herrmann JM (2007) Translocation of proteins into mitochondria. Annu Rev Biochem 76:723–749. doi:https://doi.org/10.1146/annurev.biochem.76.052705.163409CrossRefPubMed

190.

Schmidt O, Pfanner N, Meisinger C (2010) Mitochondrial protein import: from proteomics to functional mechanisms. Nat Rev Mol Cell Biol 11(9):655–667. doi:https://doi.org/10.1038/nrm2959CrossRefPubMed

191.

Saitoh T, Igura M, Obita T, Ose T, Kojima R, Maenaka K, Endo T, Kohda D (2007) Tom20 recognizes mitochondrial presequences through dynamic equilibrium among multiple bound states. Embo J 26(22):4777–4787. doi:https://doi.org/10.1038/sj.emboj.7601888CrossRefPubMedPubMedCentral

192.

Zhang F, Zhang L, Qi Y, Xu H (2016) Mitochondrial cAMP signaling. Cellular and molecular life sciences. CMLS 73(24):4577–4590. doi:https://doi.org/10.1007/s00018-016-2282-2CrossRefPubMed

193.

Zhang F, Qi Y, Zhou K, Zhang G, Linask K, Xu H (2015) The cAMP phosphodiesterase Prune localizes to the mitochondrial matrix and promotes mtDNA replication by stabilizing TFAM. EMBO Rep 16(4):520–527. doi:https://doi.org/10.15252/embr.201439636CrossRefPubMedPubMedCentral

194.

Vasseur A, Cabel L, Tredan O, Chevrier M, Dubot C, Lorgis V, Jacot W, Goncalves A, Debled M, Levy C, Ferrero JM, Jouannaud C, Luporsi E, Mouret-Reynier MA, Dalenc F, Lemonnier J, Savignoni A, Tanguy ML, Bidard FC, Pierga JY (2020) Prognostic value of CEC count in HER2-negative metastatic breast cancer patients treated with bevacizumab and chemotherapy: a prospective validation study (UCBG COMET). Angiogenesis 23(2):193–202. doi:https://doi.org/10.1007/s10456-019-09697-7CrossRefPubMed

195.

Santos JM, Tewari S, Kowluru RA (2012) A compensatory mechanism protects retinal mitochondria from initial insult in diabetic retinopathy. Free Radic Biol Med 53(9):1729–1737. doi:https://doi.org/10.1016/j.freeradbiomed.2012.08.588CrossRefPubMedPubMedCentral

196.

Santos JM, Kowluru RA (2011) Role of mitochondria biogenesis in the metabolic memory associated with the continued progression of diabetic retinopathy and its regulation by lipoic acid. Investig Ophthalmol Vis Sci 52(12):8791–8798. doi:https://doi.org/10.1167/iovs.11-8203CrossRef

197.

Santos JM, Tewari S, Goldberg AF, Kowluru RA (2011) Mitochondrial biogenesis and the development of diabetic retinopathy. Free Radic Biol Med 51(10):1849–1860. doi:https://doi.org/10.1016/j.freeradbiomed.2011.08.017CrossRefPubMedPubMedCentral

198.

Kukidome D, Nishikawa T, Sonoda K, Imoto K, Fujisawa K, Yano M, Motoshima H, Taguchi T, Matsumura T, Araki E (2006) Activation of AMP-activated protein kinase reduces hyperglycemia-induced mitochondrial reactive oxygen species production and promotes mitochondrial biogenesis in human umbilical vein endothelial cells. Diabetes 55(1):120–127CrossRef

199.

Csiszar A, Labinskyy N, Pinto JT, Ballabh P, Zhang H, Losonczy G, Pearson K, de Cabo R, Pacher P, Zhang C, Ungvari Z (2009) Resveratrol induces mitochondrial biogenesis in endothelial cells. Am J Physiol Heart Circ Physiol 297(1):H13–20. doi:https://doi.org/10.1152/ajpheart.00368.2009CrossRefPubMedPubMedCentral

200.

Tarantini S, Valcarcel-Ares MN, Toth P, Yabluchanskiy A, Tucsek Z, Kiss T, Hertelendy P, Kinter M, Ballabh P, Süle Z, Farkas E, Baur JA, Sinclair DA, Csiszar A, Ungvari Z (2019) Nicotinamide mononucleotide (NMN) supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function in aged mice. Redox Biol 24:101192. doi:https://doi.org/10.1016/j.redox.2019.101192CrossRefPubMedPubMedCentral

201.

Wang H, Ramshekar A, Kunz E, Sacks DB, Hartnett ME (2020) IQGAP1 causes choroidal neovascularization by sustaining VEGFR2-mediated Rac1 activation. Angiogenesis. https://doi.org/10.1007/s10456-020-09740-yCrossRefPubMedPubMedCentral

202.

Ungvari Z, Labinskyy N, Mukhopadhyay P, Pinto JT, Bagi Z, Ballabh P, Zhang C, Pacher P, Csiszar A (2009) Resveratrol attenuates mitochondrial oxidative stress in coronary arterial endothelial cells. Am J Physiol Heart Circ Physiol 297(5):H1876–1881. doi:https://doi.org/10.1152/ajpheart.00375.2009CrossRefPubMedPubMedCentral

203.

Santos JM, Mishra M, Kowluru RA (2014) Posttranslational modification of mitochondrial transcription factor A in impaired mitochondria biogenesis: implications in diabetic retinopathy and metabolic memory phenomenon. Exp Eye Res 121:168–177. doi:https://doi.org/10.1016/j.exer.2014.02.010CrossRefPubMedPubMedCentral

204.

Mishra M, Kowluru RA (2014) Retinal mitochondrial DNA mismatch repair in the development of diabetic retinopathy, and its continued progression after termination of hyperglycemia. Investig Ophthalmol Vis Sci 55(10):6960–6967. doi:https://doi.org/10.1167/iovs.14-15020CrossRef

205.

Yue P, Jing S, Liu L, Ma F, Zhang Y, Wang C, Duan H, Zhou K, Hua Y, Wu G, Li Y (2018) Association between mitochondrial DNA copy number and cardiovascular disease: Current evidence based on a systematic review and meta-analysis. PLoS ONE 13(11):e0206003. doi:https://doi.org/10.1371/journal.pone.0206003CrossRefPubMedPubMedCentral

206.

Ait-Aissa K, Kadlec AO, Hockenberry J, Gutterman DD, Beyer AM (2018) Telomerase reverse transcriptase protects against angiotensin II-induced microvascular endothelial dysfunction. Am J Physiol Heart Circ Physiol 314(5):H1053–h1060. doi:https://doi.org/10.1152/ajpheart.00472.2017CrossRefPubMed

207.

Kajihara N, Kukidome D, Sada K, Motoshima H, Furukawa N, Matsumura T, Nishikawa T, Araki E (2017) Low glucose induces mitochondrial reactive oxygen species via fatty acid oxidation in bovine aortic endothelial cells. J Diabetes Invest 8(6):750–761. doi:https://doi.org/10.1111/jdi.12678CrossRef

208.

Xie X, Chowdhury SR, Sangle G, Shen GX (2010) Impact of diabetes-associated lipoproteins on oxygen consumption and mitochondrial enzymes in porcine aortic endothelial cells. Acta Biochim Pol 57(4):393–398CrossRef

209.

Sangle GV, Chowdhury SK, Xie X, Stelmack GL, Halayko AJ, Shen GX (2010) Impairment of mitochondrial respiratory chain activity in aortic endothelial cells induced by glycated low-density lipoprotein. Free Radic Biol Med 48(6):781–790. doi:https://doi.org/10.1016/j.freeradbiomed.2009.12.017CrossRefPubMed

Titel: Molecular mechanisms of coronary microvascular endothelial dysfunction in diabetes mellitus: focus on mitochondrial quality surveillance
verfasst von: Danan Sun
Jin Wang
Sam Toan
David Muid
Ruibing Li
Xing Chang
Hao Zhou
Publikationsdatum: 18.03.2022
Verlag: Springer Netherlands
Erschienen in: Angiogenesis / Ausgabe 3/2022
Print ISSN: 0969-6970
Elektronische ISSN: 1573-7209
DOI: https://doi.org/10.1007/s10456-022-09835-8

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