nach oben

Erschienen in:

01.05.2020 | Original Paper

Targeting endothelial thioredoxin-interacting protein (TXNIP) protects from metabolic disorder-related impairment of vascular function and post-ischemic revascularisation

verfasst von: Alison Domingues, Catherine Boisson-Vidal, Perrine Marquet de Rouge, Blandine Dizier, Jérémy Sadoine, Virginie Mignon, Emilie Vessières, Daniel Henrion, Virginie Escriou, Pascal Bigey, Catherine Chaussain, David M. Smadja, Valérie Nivet-Antoine

Erschienen in: Angiogenesis | Ausgabe 2/2020

Einloggen, um Zugang zu erhalten

Abstract

Introduction

Although thioredoxin-interacting protein (TXNIP) is involved in a variety of biological functions, the contribution of endothelial TXNIP has not been well-defined in regards to endothelial and vascular function or in post-ischemic revascularisation. We postulated that inhibition of endothelial TXNIP with siRNA or in a Cre-LoxP system could be involved in protection from high fat, high protein, low carbohydrate (HFHPLC) diet-induced oxidative stress and endothelial dysfunction, leading to vascular damage and impaired revascularisation in vivo.

Methods and results

To investigate the role of endothelial TXNIP, the TXNIP gene was deleted in endothelial cells using anti-TXNIP siRNA treatment or the Cre-LoxP system. Murine models were fed a HFHPLC diet, known to induce metabolic disorders. Endothelial TXNIP targeting resulted in protection against metabolic disorder-related endothelial oxidative stress and endothelial dysfunction. This protective effect mitigates media cell loss induced by metabolic disorders and hampered metabolic disorder-related vascular dysfunction assessed by aortic reactivity and distensibility. In aortic ring cultures, metabolic disorders impaired vessel sprouting and this alteration was alleviated by deletion of endothelial TXNIP. When subjected to ischemia, mice fed a HFHPLC diet exhibited defective post-ischemic angiogenesis and impaired blood flow recovery in hind limb ischemia. However, reducing endothelial TXNIP rescued metabolic disorder-related impairment of ischemia-induced revascularisation.

Conclusion

Collectively, these results show that targeting endothelial TXNIP in metabolic disorders is essential to maintaining endothelial function, vascular function and improving ischemia-induced revascularisation, making TXNIP a potential therapeutic target for therapy of vascular complications related to metabolic disorders.

Nur mit Berechtigung zugänglich

Clifton P (2009) High protein diets and weight control. Nutr Metab Cardiovasc Dis 19:379–382. https://doi.org/10.1016/j.numecd.2009.02.011 CrossRefPubMed

Bedarida T, Baron S, Vessieres E et al (2014) High-protein-low-carbohydrate diet: deleterious metabolic and cardiovascular effects depend on age. Am J Physiol Heart Circ Physiol 307:H649–H657. https://doi.org/10.1152/ajpheart.00291.2014 CrossRefPubMed

Burcelin R, Crivelli V, Dacosta A et al (2002) Heterogeneous metabolic adaptation of C57BL/6J mice to high-fat diet. Am J Physiol Endocrinol Metab 282:E834–E842. https://doi.org/10.1152/ajpendo.00332.2001 CrossRefPubMed

Foo SY, Heller ER, Wykrzykowska J et al (2009) Vascular effects of a low-carbohydrate high-protein diet. Proc Natl Acad Sci USA 106:15418–15423. https://doi.org/10.1073/pnas.0907995106 CrossRefPubMedPubMedCentral

Garg PK, Biggs ML, Carnethon M et al (2014) Metabolic syndrome and risk of incident peripheral artery disease. Hypertension 63:413–419. https://doi.org/10.1161/HYPERTENSIONAHA.113.01925 CrossRefPubMed

Richter L, Freisinger E, Lüders F et al (2018) Impact of diabetes type on treatment and outcome of patients with peripheral artery disease. Diabetes Vasc Dis Res 15:504–510. https://doi.org/10.1177/1479164118793986 CrossRef

Incalza MA, D'Oria R, Natalicchio A et al (2018) Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases. Vasc Pharmacol 100:1–19. https://doi.org/10.1016/j.vph.2017.05.005 CrossRef

Jia G, Sowers JR (2014) Endothelial dysfunction potentially interacts with impaired glucose metabolism to increase cardiovascular risk. Hypertension 64:1192–1193. https://doi.org/10.1161/HYPERTENSIONAHA.114.04348 CrossRefPubMed

Dawber TR, Meadors GF, Moore FE (1951) Epidemiological approaches to heart disease: the Framingham Study. Am J Public Health Nations Health 41:279–281. https://doi.org/10.2105/ajph.41.3.279 CrossRefPubMedPubMedCentral

10.

Ungvari Z, Tarantini S, Kiss T et al (2018) Endothelial dysfunction and angiogenesis impairment in the ageing vasculature. Nat Rev Cardiol 15:555–565. https://doi.org/10.1038/s41569-018-0030-z CrossRefPubMedPubMedCentral

11.

Albadawi H, Oklu R, Cormier NR et al (2014) Hind limb ischemia-reperfusion injury in diet-induced obese mice. J Surg Res 190:683–691. https://doi.org/10.1016/j.jss.2014.01.020 CrossRefPubMedPubMedCentral

12.

Couffinhal T, Silver M, Kearney M et al (1999) Impaired collateral vessel development associated with reduced expression of vascular endothelial growth factor in ApoE-/- mice. Circulation 99:3188–3198. https://doi.org/10.1161/01.cir.99.24.3188 CrossRefPubMed

13.

Bir SC, Pattillo CB, Pardue S et al (2014) Nitrite anion therapy protects against chronic ischemic tissue injury in db/db diabetic mice in a NO/VEGF-dependent manner. Diabetes 63:270–281. https://doi.org/10.2337/db13-0890 CrossRefPubMed

14.

Silvestre J-S, Smadja DM, Lévy BI (2013) Postischemic revascularization: from cellular and molecular mechanisms to clinical applications. Physiol Rev 93:1743–1802. https://doi.org/10.1152/physrev.00006.2013 CrossRefPubMed

15.

Cai H, Harrison DG (2000) Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res 87:840–844. https://doi.org/10.1161/01.res.87.10.840 CrossRefPubMed

16.

Collins AR, Lyon CJ, Xia X et al (2009) Age-accelerated atherosclerosis correlates with failure to upregulate antioxidant genes. Circ Res 104:e42–e54. https://doi.org/10.1161/CIRCRESAHA.108.188771 CrossRefPubMed

17.

Csiszar A, Ungvari Z, Edwards JG et al (2002) Aging-induced phenotypic changes and oxidative stress impair coronary arteriolar function. Circ Res 90:1159–1166. https://doi.org/10.1161/01.res.0000020401.61826.ea CrossRefPubMed

18.

Nivet-Antoine V, Labat C, Shamieh El S et al (2013) Relationship between catalase haplotype and arterial aging. Atherosclerosis 227:100–105. https://doi.org/10.1016/j.atherosclerosis.2012.12.015 CrossRefPubMed

19.

Ebrahimian TG, Heymes C, You D et al (2006) NADPH oxidase-derived overproduction of reactive oxygen species impairs postischemic neovascularization in mice with type 1 diabetes. Am J Pathol 169:719–728. https://doi.org/10.2353/ajpath.2006.060042 CrossRefPubMedPubMedCentral

20.

Haddad P, Dussault S, Groleau J et al (2011) Nox2-derived reactive oxygen species contribute to hypercholesterolemia-induced inhibition of neovascularization: effects on endothelial progenitor cells and mature endothelial cells. Atherosclerosis 217:340–349. https://doi.org/10.1016/j.atherosclerosis.2011.03.038 CrossRefPubMed

21.

Warren CM, Ziyad S, Briot A et al (2014) A ligand-independent VEGFR2 signaling pathway limits angiogenic responses in diabetes. Sci Signal 7:ra1. https://doi.org/10.1126/scisignal.2004235 CrossRefPubMedPubMedCentral

22.

Houstis N, Rosen ED, Lander ES (2006) Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature 440:944–948. https://doi.org/10.1038/nature04634 CrossRefPubMed

23.

Hebert-Schuster M, Fabre EE, Nivet-Antoine V (2012) Catalase polymorphisms and metabolic diseases. Curr Opin Clin Nutr Metab Care 15:397–402. https://doi.org/10.1097/MCO.0b013e328354a326 CrossRefPubMed

24.

Junn E, Han SH, Im JY et al (2000) Vitamin D3 up-regulated protein 1 mediates oxidative stress via suppressing the thioredoxin function. J Immunol 164:6287–6295. https://doi.org/10.4049/jimmunol.164.12.6287 CrossRefPubMed

25.

Kim GS, Jung JE, Narasimhan P et al (2012) Induction of thioredoxin-interacting protein is mediated by oxidative stress, calcium, and glucose after brain injury in mice. Neurobiol Dis 46:440–449. https://doi.org/10.1016/j.nbd.2012.02.008 CrossRefPubMedPubMedCentral

26.

Bedarida T, Baron S, Vibert F et al (2016) Resveratrol decreases TXNIP mRNA and protein nuclear expressions with an arterial function improvement in old mice. J Gerontol A 71:720–729. https://doi.org/10.1093/gerona/glv071 CrossRef

27.

Shah A, Xia L, Goldberg H et al (2013) Thioredoxin-interacting protein mediates high glucose-induced reactive oxygen species generation by mitochondria and the NADPH oxidase, Nox4, in mesangial cells. J Biol Chem 288:6835–6848. https://doi.org/10.1074/jbc.M112.419101 CrossRefPubMedPubMedCentral

28.

Schulze PC, Yoshioka J, Takahashi T et al (2004) Hyperglycemia promotes oxidative stress through inhibition of thioredoxin function by thioredoxin-interacting protein. J Biol Chem 279:30369–30374. https://doi.org/10.1074/jbc.M400549200 CrossRefPubMed

29.

Nivet-Antoine V, Cottart C-H, Lemaréchal H et al (2010) Trans-resveratrol downregulates Txnip overexpression occurring during liver ischemia-reperfusion. Biochimie 92:1766–1771. https://doi.org/10.1016/j.biochi.2010.07.018 CrossRefPubMed

30.

Oberacker T, Bajorat J, Ziola S et al (2018) Enhanced expression of thioredoxin-interacting-protein regulates oxidative DNA damage and aging. FEBS Lett 592:2297–2307. https://doi.org/10.1002/1873-3468.13156 CrossRefPubMedPubMedCentral

31.

Bedarida T, Domingues A, Baron S et al (2018) Reduced endothelial thioredoxin-interacting protein protects arteries from damage induced by metabolic stress in vivo. FASEB J 32:3108–3118. https://doi.org/10.1096/fj.201700856RRR CrossRefPubMed

32.

Zhou R, Tardivel A, Thorens B et al (2010) Thioredoxin-interacting protein links oxidative stress to inflammasome activation. Nature Immunol 11:136–140. https://doi.org/10.1038/ni.1831 CrossRef

33.

Zhou J, Yu Q, Chng W-J (2011) TXNIP (VDUP-1, TBP-2): a major redox regulator commonly suppressed in cancer by epigenetic mechanisms. Int J Biochem Cell Biol 43:1668–1673. https://doi.org/10.1016/j.biocel.2011.09.005 CrossRefPubMed

34.

Parikh H, Carlsson E, Chutkow WA et al (2007) TXNIP regulates peripheral glucose metabolism in humans. PLoS Med 4:e158. https://doi.org/10.1371/journal.pmed.0040158 CrossRefPubMedPubMedCentral

35.

Dunn LL, Simpson PJL, Prosser HC et al (2014) A critical role for thioredoxin-interacting protein in diabetes-related impairment of angiogenesis. Diabetes 63:675–687. https://doi.org/10.2337/db13-0417 CrossRefPubMedPubMedCentral

36.

Elshaer SL, Mohamed IN, Coucha M et al (2017) Deletion of TXNIP mitigates high-fat diet-impaired angiogenesis and prevents inflammation in a mouse model of critical limb ischemia. Antioxidants 6:E47. https://doi.org/10.3390/antiox6030047 CrossRefPubMed

37.

Jeong M, Piao Z-H, Kim MS et al (2009) Thioredoxin-interacting protein regulates hematopoietic stem cell quiescence and mobilization under stress conditions. J Immunol 183:2495–2505. https://doi.org/10.4049/jimmunol.0804221 CrossRefPubMed

38.

Arruda DC, Schlegel A, Bigey P, Escriou V (2016) Lipoplexes strengthened by anionic polymers: easy preparation of highly effective siRNA vectors based on cationic lipids and anionic polymers. Methods Mol Biol 1445:137–148. https://doi.org/10.1007/978-1-4939-3718-9_8 CrossRefPubMed

39.

Alva JA, Zovein AC, Monvoisin A et al (2006) VE-Cadherin-Cre-recombinase transgenic mouse: a tool for lineage analysis and gene deletion in endothelial cells. Dev Dyn 235:759–767. https://doi.org/10.1002/dvdy.20643 CrossRefPubMed

40.

Yoshioka J, Chutkow WA, Lee S et al (2012) Deletion of thioredoxin-interacting protein in mice impairs mitochondrial function but protects the myocardium from ischemia-reperfusion injury. J Clin Investig 122:267–279. https://doi.org/10.1172/JCI44927 CrossRefPubMed

41.

Shireman PK, Quinones MP (2005) Differential necrosis despite similar perfusion in mouse strains after ischemia. J Surg Res 129:242–250. https://doi.org/10.1016/j.jss.2005.06.013 CrossRefPubMed

42.

Nebuloni L, Kuhn GA, Müller R (2013) A comparative analysis of water-soluble and blood-pool contrast agents for in vivo vascular imaging with micro-CT. Acad Radiol 20:1247–1255. https://doi.org/10.1016/j.acra.2013.06.003 CrossRefPubMed

43.

Baker M, Robinson SD, Lechertier T et al (2011) Use of the mouse aortic ring assay to study angiogenesis. Nat Protoc 7:89–104. https://doi.org/10.1038/nprot.2011.435 CrossRefPubMed

44.

Cha-Molstad H, Saxena G, Chen J, Shalev A (2009) Glucose-stimulated expression of Txnip is mediated by carbohydrate response element-binding protein, p300, and histone H4 acetylation in pancreatic beta cells. J Biol Chem 284:16898–16905. https://doi.org/10.1074/jbc.M109.010504 CrossRefPubMedPubMedCentral

45.

Baron S, Bedarida T, Cottart C-H et al (2014) Dual effects of resveratrol on arterial damage induced by insulin resistance in aged mice. J Gerontol A 69:260–269. https://doi.org/10.1093/gerona/glt081 CrossRef

46.

Sun J, Deng H, Zhou Z et al (2018) Endothelium as a potential target for treatment of abdominal aortic aneurysm. Oxid Med Cell Longev 2018:6306542–6306612. https://doi.org/10.1155/2018/6306542 CrossRefPubMedPubMedCentral

47.

Wu D, Ren P, Zheng Y et al (2017) NLRP3 (nucleotide oligomerization domain–like receptor family, pyrin domain containing 3)–caspase-1 inflammasome degrades contractile proteins. Arterioscler Thromb Vasc Biol 37:694–706. https://doi.org/10.1161/ATVBAHA.116.307648 CrossRefPubMedPubMedCentral

48.

Gao L, Siu KL, Chalupsky K et al (2012) Role of uncoupled endothelial nitric oxide synthase in abdominal aortic aneurysm formation. Hypertension 59:158–166. https://doi.org/10.1161/HYPERTENSIONAHA.111.181644 CrossRefPubMed

49.

Siu KL, Li Q, Zhang Y et al (2017) NOX isoforms in the development of abdominal aortic aneurysm. Redox Biol 11:118–125. https://doi.org/10.1016/j.redox.2016.11.002 CrossRefPubMed

50.

Moon SK, Thompson LJ, Madamanchi N et al (2001) Aging, oxidative responses, and proliferative capacity in cultured mouse aortic smooth muscle cells. Am J Physiol Heart Circ Physiol 280:H2779–H2788. https://doi.org/10.1152/ajpheart.2001.280.6.H2779 CrossRefPubMed

51.

Gaubert ML, Sigaudo-Roussel D, Tartas M et al (2007) Endothelium-derived hyperpolarizing factor as an in vivo back-up mechanism in the cutaneous microcirculation in old mice. J Physiol 585:617–626. https://doi.org/10.1113/jphysiol.2007.143750 CrossRefPubMedPubMedCentral

52.

Gendron M-È, Thorin-Trescases N, Villeneuve L, Thorin E (2007) Aging associated with mild dyslipidemia reveals that COX-2 preserves dilation despite endothelial dysfunction. Am J Physiol Heart Circ Physiol 292:H451–H458. https://doi.org/10.1152/ajpheart.00551.2006 CrossRefPubMed

53.

Forrester MT, Seth D, Hausladen A et al (2009) Thioredoxin-interacting protein (Txnip) is a feedback regulator of S-nitrosylation. J Biol Chem 284:36160–36166. https://doi.org/10.1074/jbc.M109.057729 CrossRefPubMedPubMedCentral

54.

Hattori K, Heissig B, Wu Y et al (2002) Placental growth factor reconstitutes hematopoiesis by recruiting VEGFR1(+) stem cells from bone-marrow microenvironment. Nat Med 8:841–849. https://doi.org/10.1038/nm740 CrossRefPubMedPubMedCentral

55.

Takahashi T, Kalka C, Masuda H et al (1999) Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med 5:434–438CrossRefPubMed

56.

Nowak-Sliwinska P, Alitalo K, Allen E et al (2018) Consensus guidelines for the use and interpretation of angiogenesis assays. Angiogenesis 21:425–532. https://doi.org/10.1007/s10456-018-9613-x CrossRefPubMedPubMedCentral

57.

Farrell MR, Rogers LK, Liu Y et al (2010) Thioredoxin-interacting protein inhibits hypoxia-inducible factor transcriptional activity. Free Radic Biol Med 49:1361–1367. https://doi.org/10.1016/j.freeradbiomed.2010.07.016 CrossRefPubMedPubMedCentral

58.

Shin D, Jeon JH, Jeong M et al (2008) VDUP1 mediates nuclear export of HIF1alpha via CRM1-dependent pathway. Biochim Biophys Acta 1783:838–848. https://doi.org/10.1016/j.bbamcr.2007.10.012 CrossRefPubMed

59.

Simons M, Alitalo K, Annex BH et al (2015) State-of-the-art methods for evaluation of angiogenesis and tissue vascularization: a scientific statement from the American Heart Association. Circ Res 116:e99–e132. https://doi.org/10.1161/RES.0000000000000054 CrossRefPubMedPubMedCentral

60.

Das NM, Hatsell S, Nannuru K et al (2016) In vivo quantitative microcomputed tomographic analysis of vasculature and organs in a normal and diseased mouse model. PLoS ONE 11:e0150085–e0150118. https://doi.org/10.1371/journal.pone.0150085 CrossRefPubMedPubMedCentral

61.

Joseph C, Quach JM, Walkley CR et al (2013) Deciphering hematopoietic stem cells in their niches: a critical appraisal of genetic models, lineage tracing, and imaging strategies. Cell Stem Cell 13:520–533. https://doi.org/10.1016/j.stem.2013.10.010 CrossRefPubMed

62.

Kogata N, Arai Y, Pearson JT et al (2006) Cardiac ischemia activates vascular endothelial cadherin promoter in both preexisting vascular cells and bone marrow cells involved in neovascularization. Circ Res 98:897–904. https://doi.org/10.1161/01.RES.0000218193.51136.ad CrossRefPubMed

63.

Kilani B, Gourdou Latyszenok V, Guy A et al (2019) Comparison of endothelial promoter efficiency and specificity in mice reveals a subset of Pdgfb-positive hematopoietic cells. J Thromb Haemost 17:827–840. https://doi.org/10.1111/jth.14417 CrossRefPubMed

64.

Guerin CL, Loyer X, Vilar J et al (2015) Bone-marrow-derived very small embryonic-like stem cells in patients with critical leg ischaemia: evidence of vasculogenic potential. Thromb Haemost 113:1084–1094. https://doi.org/10.1160/TH14-09-0748 CrossRefPubMed

65.

Smadja DM (2017) Bone marrow very small embryonic-like stem cells: new generation of autologous cell therapy soon ready for prime time? Stem Cell Rev Rep 13:198–201. https://doi.org/10.1007/s12015-017-9718-4 CrossRefPubMed

66.

Rossi E, Poirault-Chassac S, Bieche I et al (2019) Human endothelial colony forming cells express intracellular CD133 that modulates their vasculogenic properties. Stem Cell Rev Rep 15:590–600. https://doi.org/10.1007/s12015-019-09881-8 CrossRefPubMed

Titel: Targeting endothelial thioredoxin-interacting protein (TXNIP) protects from metabolic disorder-related impairment of vascular function and post-ischemic revascularisation
verfasst von: Alison Domingues
Catherine Boisson-Vidal
Perrine Marquet de Rouge
Blandine Dizier
Jérémy Sadoine
Virginie Mignon
Emilie Vessières
Daniel Henrion
Virginie Escriou
Pascal Bigey
Catherine Chaussain
David M. Smadja
Valérie Nivet-Antoine
Publikationsdatum: 01.05.2020
Verlag: Springer Netherlands
Erschienen in: Angiogenesis / Ausgabe 2/2020
Print ISSN: 0969-6970
Elektronische ISSN: 1573-7209
DOI: https://doi.org/10.1007/s10456-019-09704-x

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Targeting endothelial thioredoxin-interacting protein (TXNIP) protects from metabolic disorder-related impairment of vascular function and post-ischemic revascularisation