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Cardiovascular Drugs and Therapy

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26.07.2021 | Original Article

Flavocoxid Ameliorates Aortic Calcification Induced by Hypervitaminosis D₃ and Nicotine in Rats Via Targeting TNF-α, IL-1β, iNOS, and Osteogenic Runx2

verfasst von: Ahmed E. Amer, George S. G. Shehatou, Hassan A. El-Kashef, Manar A. Nader, Ahmed R. El-Sheakh

Erschienen in: Cardiovascular Drugs and Therapy | Ausgabe 6/2022

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Abstract

Purpose

This research was designed to investigate the effects and mechanisms of flavocoxid (FCX) on vascular calcification (VC) in rats.

Methods

Vitamin D₃ and nicotine were administered to Wistar rats, which then received FCX (VC-FCX group) or its vehicle (VC group) for 4 weeks. Control and FCX groups served as controls. Systolic (SBP) and diastolic (DBP) blood pressures, heart rate (HR), and left ventricular weight (LVW)/BW were measured. Serum concentrations of calcium, phosphate, creatinine, uric acid, and alkaline phosphatase were determined. Moreover, aortic calcium content and aortic expression of runt-related transcription factor (Runx2), osteopontin (OPN), Il-1β, α-smooth muscle actin (α-SMA), matrix metalloproteinase-9 (MMP-9), inducible nitric oxide synthase (iNOS), and tumor necrosis factor-α (TNF-α) were assessed. Oxidative status in aortic homogenates was investigated.

Results

Compared to untreated VC rats, FCX treatment prevented body weight loss, reduced aortic calcium deposition, restored normal values of SBP, DBP, and HR, and attenuated LV hypertrophy. FCX also improved renal function and ameliorated serum levels of phosphorus, calcium, and ALP in rats with VC. FCX abolished aortic lipid peroxidation in VC rats. Moreover, VC-FCX rats showed marked reductions in aortic levels of Il-1β and osteogenic marker (Runx2) and attenuated aortic expression of TNF-α, iNOS, and MMP-9 proteins compared to untreated VC rats. The expression of the smooth muscle lineage marker α-SMA was greatly enhanced in aortas from VC rats upon FCX treatment.

Conclusion

These findings demonstrate FCX ability to attenuate VDN-induced aortic calcinosis in rats, suggesting its potential for preventing arteiocalcinosis in diabetic patients and those with chronic kidney disease.

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Leem J, Lee IK. Mechanisms of vascular calcification: the pivotal role of pyruvate dehydrogenase kinase 4. Endocrinol Metab (Seoul). 2016;31(1):52–61.CrossRef

Mackey RH, Venkitachalam L, Sutton-Tyrrell K. Calcifications, arterial stiffness and atherosclerosis. Adv Cardiol. 2007;44:234–44.PubMedCrossRef

Fishbein MC, Fishbein GA. Arteriosclerosis: facts and fancy. Cardiovasc Pathol. 2015;24(6):335–42.PubMedCrossRef

Ho CY, Shanahan CM. Medial arterial calcification: an overlooked player in peripheral arterial disease. Arterioscler Thromb Vasc Biol. 2016;36(8):1475–82.PubMedCrossRef

Vattikuti R, Towler DA. Osteogenic regulation of vascular calcification: an early perspective. Am J Physiol-Endocrinol Metabol. 2004;286(5):E686–E96.CrossRef

Shanahan CM, Crouthamel MH, Kapustin A, Giachelli CM. Arterial calcification in chronic kidney disease: key roles for calcium and phosphate. Circ Res. 2011;109(6):697–711.PubMedPubMedCentralCrossRef

Paloian NJ, Giachelli CM. A current understanding of vascular calcification in CKD. Am J Physiol-Renal Physiol. 2014;307(8):F891–900.PubMedPubMedCentralCrossRef

Mavridis G, Souliou E, Diza E, Symeonidis G, Pastore F, Vassiliou AM, et al. Inflammatory cytokines in insulin-treated patients with type 2 diabetes. Nutr Metab Cardiovasc Dis. 2008;18(7):471–6.PubMedCrossRef

Yamada S, Taniguchi M, Tokumoto M, Toyonaga J, Fujisaki K, Suehiro T, et al. The antioxidant tempol ameliorates arterial medial calcification in uremic rats: important role of oxidative stress in the pathogenesis of vascular calcification in chronic kidney disease. J Bone Miner Res. 2012;27(2):474–85.PubMedCrossRef

10.

Gaillard V, Casellas D, Seguin-Devaux C, Schohn H, Dauça M, Atkinson J, et al. Pioglitazone improves aortic wall elasticity in a rat model of elastocalcinotic arteriosclerosis. Hypertension. 2005;46(2):372–9.PubMedCrossRef

11.

Thompson B, Towler DA. Arterial calcification and bone physiology: role of the bone–vascular axis. Nat Rev Endocrinol. 2012;8(9):529.PubMedPubMedCentralCrossRef

12.

Byon CH, Javed A, Dai Q, Kappes JC, Clemens TL, Darley-Usmar VM, et al. Oxidative stress induces vascular calcification through modulation of the osteogenic transcription factor Runx2 by AKT signaling. J Biol Chem. 2008;283(22):15319–27.PubMedPubMedCentralCrossRef

13.

Massy ZA, Maziere C, Kamel S, Brazier M, Choukroun G, Tribouilloy C, et al. Impact of inflammation and oxidative stress on vascular calcifications in chronic kidney disease. Pediatr Nephrol. 2005;20(3):380–2.PubMedCrossRef

14.

Bessueille L, Magne D. Inflammation: a culprit for vascular calcification in atherosclerosis and diabetes. Cell Mol Life Sci. 2015;72(13):2475–89.PubMedCrossRef

15.

Bondm C. Inhibition of transcription factor NF-kappaB reduces matrix metalloproteinase-1, -3 and -9 production by vascular smooth muscle cells. Cardiovasc Res. 2001;50(3):556.CrossRef

16.

Chang X-y, Cui L, Wang X-z, Zhang L, Zhu D, Zhou X-r, et al. Quercetin attenuates vascular calcification through suppressed oxidative stress in adenine-induced chronic renal failure rats. Biomed Res Int 2017;2017:5716204.

17.

Basalyga DM, Simionescu DT, Xiong W, Baxter BT, Starcher BC, Vyavahare NR. Elastin degradation and calcification in an abdominal aorta injury model: role of matrix metalloproteinases. Circulation. 2004;110(22):3480–7.PubMedPubMedCentralCrossRef

18.

Pai A, Leaf EM, El-Abbadi M, Giachelli CM. Elastin degradation and vascular smooth muscle cell phenotype change precede cell loss and arterial medial calcification in a uremic mouse model of chronic kidney disease. Am J Pathol. 2011;178(2):764–73.PubMedPubMedCentralCrossRef

19.

Niederhoffer N, Bobryshev YV, Lartaud-Idjouadiene I, Giummelly P, Atkinson J. Aortic calcification produced by vitamin D3 plus nicotine. J Vasc Res. 1997;34(5):386–98.PubMedCrossRef

20.

Gong C, Li L, Qin C, Wu W, Liu Q, Li Y, et al. The involvement of Notch1-RBP-Jk/Msx2 signaling pathway in aortic calcification of diabetic nephropathy rats. Journal of diabetes research. 2017;2017:8968523.PubMedPubMedCentralCrossRef

21.

Tang F, Chen S, Wu X, Wang T, Chen J, Li J, et al. Hypercholesterolemia accelerates vascular calcification induced by excessive vitamin D via oxidative stress. Calcif Tissue Int. 2006;79(5):326–39.PubMedCrossRef

22.

Wallin R, Wajih N, Greenwood GT, Sane DC. Arterial calcification: a review of mechanisms, animal models, and the prospects for therapy. Med Res Rev. 2001;21(4):274–301.PubMedCrossRef

23.

Burnett B, Jia Q, Zhao Y, Levy R. A medicinal extract of Scutellaria baicalensis and Acacia catechu acts as a dual inhibitor of cyclooxygenase and 5-lipoxygenase to reduce inflammation. J Med Food. 2007;10(3):442–51.PubMedCrossRef

24.

Altavilla D, Squadrito F, Bitto A, Polito F, Burnett B, Di Stefano V, et al. Flavocoxid, a dual inhibitor of cyclooxygenase and 5-lipoxygenase, blunts pro-inflammatory phenotype activation in endotoxin-stimulated macrophages. Br J Pharmacol. 2009;157(8):1410–8.PubMedPubMedCentralCrossRef

25.

Burnett BP, Bitto A, Altavilla D, Squadrito F, Levy RM, Pillai L. Flavocoxid inhibits phospholipase A2, peroxidase moieties of the cyclooxygenases (COX), and 5-lipoxygenase, modifies COX-2 gene expression, and acts as an antioxidant. Mediat Inflamm. 2011;2011:385780.CrossRef

26.

Messina S, Bitto A, Aguennouz M, Mazzeo A, Migliorato A, Polito F, et al. Flavocoxid counteracts muscle necrosis and improves functional properties in mdx mice: a comparison study with methylprednisolone. Exp Neurol. 2009;220(2):349–58.PubMedCrossRef

27.

Polito F, Bitto A, Irrera N, Squadrito F, Fazzari C, Minutoli L, et al. Flavocoxid, a dual inhibitor of cyclooxygenase-2 and 5-lipoxygenase, reduces pancreatic damage in an experimental model of acute pancreatitis. Br J Pharmacol. 2010;161(5):1002–11.PubMedPubMedCentralCrossRef

28.

Bitto A, Minutoli L, David A, Irrera N, Rinaldi M, Venuti FS, et al. Flavocoxid, a dual inhibitor of COX-2 and 5-LOX of natural origin, attenuates the inflammatory response and protects mice from sepsis. Crit Care. 2012;16(1):R32.PubMedPubMedCentralCrossRef

29.

El-Kashef DH, El-Kenawi AE, Suddek GM, Salem HA. Flavocoxid attenuates gentamicin-induced nephrotoxicity in rats. Naunyn Schmiedeberg's Arch Pharmacol. 2015;388(12):1305–15.CrossRef

30.

Abdеlaziz RR, Еlmahdy MK, Suddek GM. Flavocoxid attenuates airway inflammation in ovalbumin-induced mouse asthma model. Chem Biol Interact. 2018;292:15–23.CrossRef

31.

Micali A, Pallio G, Irrera N, Marini H, Trichilo V, Puzzolo D, et al. Flavocoxid, a natural antioxidant, protects mouse kidney from cadmium-induced toxicity. Oxidative Med Cell Longev. 2018;2018:9162946.CrossRef

32.

Singh DP, Chopra K. Flavocoxid, dual inhibitor of cyclooxygenase-2 and 5-lipoxygenase, exhibits neuroprotection in rat model of ischaemic stroke. Pharmacol Biochem Behav. 2014;120:33–42.PubMedCrossRef

33.

El-Sheakh AR, Ghoneim HA, Suddek GM, el SM A. Antioxidant and anti-inflammatory effects of flavocoxid in high-cholesterol-fed rabbits. Naunyn Schmiedeberg's Arch Pharmacol. 2015;388(12):1333–44.CrossRef

34.

Ding L, Jia C, Zhang Y, Wang W, Zhu W, Chen Y, et al. Baicalin relaxes vascular smooth muscle and lowers blood pressure in spontaneously hypertensive rats. Biomed Pharmacother. 2019;111:325–30.PubMedCrossRef

35.

Ku SK, Bae JS. Baicalin, baicalein and wogonin inhibits high glucose-induced vascular inflammation in vitro and in vivo. BMB Rep. 2015;48(9):519–24.PubMedPubMedCentralCrossRef

36.

Ihm SH, Lee JO, Kim SJ, Seung KB, Schini-Kerth VB, Chang K, et al. Catechin prevents endothelial dysfunction in the prediabetic stage of OLETF rats by reducing vascular NADPH oxidase activity and expression. Atherosclerosis. 2009;206(1):47–53.PubMedCrossRef

37.

Koga T, Meydani M. Effect of plasma metabolites of (+)-catechin and quercetin on monocyte adhesion to human aortic endothelial cells. Am J Clin Nutr. 2001;73(5):941–8.PubMedCrossRef

38.

Zhang J, Chang J-R, Duan X-H, Yu Y-R, Zhang B-H. Thyroid hormone attenuates vascular calcification induced by vitamin D3 plus nicotine in rats. Calcif Tissue Int. 2015;96(1):80–7.PubMedCrossRef

39.

Atkinson J, Poitevin P, Chillon JM, Lartaud I, Levy B. Vascular ca overload produced by vitamin D3 plus nicotine diminishes arterial distensibility in rats. Am J Phys. 1994;266(2 Pt 2):H540–7.

40.

Morgan SL, Baggott JE, Moreland L, Desmond R, Kendrach AC. The safety of flavocoxid, a medical food, in the dietary management of knee osteoarthritis. J Med Food. 2009;12(5):1143–8.PubMedPubMedCentralCrossRef

41.

Burnett BP, Silva S, Mesches MH, Wilson S, Jia Q. Safety evaluation of a combination, defined extract of Scutellaria baicalensis and Acacia catechu. Journal of Food Biochemistry. 2007;31(6):797–825.

42.

Minutoli L, Marini H, Rinaldi M, Bitto A, Irrera N, Pizzino G, et al. A dual inhibitor of cyclooxygenase and 5-lipoxygenase protects against kainic acid-induced brain injury. NeuroMolecular Med. 2015;17(2):192–201.PubMedCrossRef

43.

Thorin E, Henrion D, Oster L, Thorin-Trescases N, Capdeville C, Martin JA, et al. Vascular calcium overload produced by administration of vitamin D3 and nicotine in rats. Changes in tissue calcium levels, blood pressure, and pressor responses to electrical stimulation or norepinephrine in vivo. J Cardiovasc Pharmacol. 1990;16(2):257–66.PubMedCrossRef

44.

Wu SY, Pan CS, Geng B, Zhao J, Yu F, Pang YZ, et al. Hydrogen sulfide ameliorates vascular calcification induced by vitamin D3 plus nicotine in rats 1. Acta Pharmacol Sin. 2006;27(3):299–306.PubMedCrossRef

45.

Holmar J, Noels H, Bohm M, Bhargava S, Jankowski J, Orth-Alampour S. Development, establishment and validation of in vitro and ex vivo assays of vascular calcification. Biochem Biophys Res Commun. 2020;530(2):462–70.PubMedCrossRef

46.

Amin FM, Abdelaziz RR, Hamed MF, Nader MA, Shehatou GSG. Dimethyl fumarate ameliorates diabetes-associated vascular complications through ROS-TXNIP-NLRP3 inflammasome pathway. Life Sci. 2020;256:117887.PubMedCrossRef

47.

Neumann L, Mueller M, Moos V, Heller F, Meyer TF, Loddenkemper C, et al. Mucosal inducible NO synthase-producing IgA+ plasma cells in helicobacter pylori-infected patients. J Immunol. 2016;197(5):1801–8.PubMedPubMedCentralCrossRef

48.

Tsai TH, Chai HT, Sun CK, Yen CH, Leu S, Chen YL, et al. Obesity suppresses circulating level and function of endothelial progenitor cells and heart function. J Transl Med. 2012;10:137.PubMedPubMedCentralCrossRef

49.

Konopelski P, Ufnal M. Electrocardiography in rats: a comparison to human. Physiol Res. 2016;65(5):717–25.PubMedCrossRef

50.

Moe SM, Chen NX. Pathophysiology of vascular calcification in chronic kidney disease. Circ Res. 2004;95(6):560–7.PubMedCrossRef

51.

Shao J-S, Cheng S-L, Sadhu J, Towler DA. Inflammation and the osteogenic regulation of vascular calcification: a review and perspective. Hypertension. 2010;55(3):579–92.PubMedCrossRef

52.

Cai Y, Teng X, Pan C-S, Duan X-H, Tang C-S, Qi Y-F. Adrenomedullin up-regulates osteopontin and attenuates vascular calcification via the cAMP/PKA signaling pathway. Acta Pharmacol Sin. 2010;31(10):1359.PubMedPubMedCentralCrossRef

53.

G-z L, Jiang W, Zhao J, Pan C-s, Cao J, C-s T, et al. Ghrelin blunted vascular calcification in vivo and in vitro in rats. Regul Pept. 2005;129(1–3):167–76.

54.

Chavhan SG, Brar RS, Banga HS, Sandhu HS, Sodhi S, Gadhave PD, et al. Clinicopathological studies on vitamin D(3) toxicity and therapeutic evaluation of Aloe vera in rats. Toxicol Int. 2011;18(1):35–43.PubMedPubMedCentralCrossRef

55.

Khosravi ZS, Kafeshani M, Tavasoli P, Zadeh AH, Entezari MH. Effect of vitamin D supplementation on weight loss, glycemic indices, and lipid profile in obese and overweight women: a clinical trial study. Int J Prev Med. 2018;9:63.PubMedPubMedCentralCrossRef

56.

Shi Y, Wang S, Peng H, Lv Y, Li W, Cheng S, et al. Fibroblast growth factor 21 attenuates vascular calcification by alleviating endoplasmic reticulum stress mediated apoptosis in rats. Int J Biol Sci. 2019;15(1):138–47.PubMedPubMedCentralCrossRef

57.

Yang R, Teng X, Li H, Xue H-M, Guo Q, Xiao L, et al. Hydrogen sulfide improves vascular calcification in rats by inhibiting endoplasmic reticulum stress. Oxidative Med Cell Longev. 2016;2016:9095242.CrossRef

58.

Liu Y, Zhou YB, Zhang GG, Cai Y, Duan XH, Teng X, et al. Cortistatin attenuates vascular calcification in rats. Regul Pept. 2010;159(1–3):35–43.PubMedCrossRef

59.

Lartaud-Idjouadiene I, Lompré A-M, Kieffer P. Colas Trs, Atkinson J. cardiac consequences of prolonged exposure to an isolated increase in aortic stiffness. Hypertension. 1999;34(1):63–9.PubMedCrossRef

60.

Niederhoffer N, Lartaud-Idjouadiene I, Giummelly P, Duvivier C, Peslin R, Atkinson J. Calcification of medial elastic fibers and aortic elasticity. Hypertension. 1997;29(4):999–1006.PubMedCrossRef

61.

Lartaud-Idjouadiene I, Niederhoffer N, Debets J, Struyker-Boudier H, Atkinson J, Smits J. Cardiac function in a rat model of chronic aortic stiffness. Am J Phys Heart Circ Phys. 1997;272(5):H2211–H8.

62.

Shi Y-C, Lu W-W, Hou Y-L, Fu K, Gan F, Cheng S-J, et al. Protection effect of exogenous fibroblast growth factor 21 on the kidney injury in vascular calcification rats. Chin Med J. 2018;131(5):532.PubMedPubMedCentralCrossRef

63.

Stabley JN, Towler DA. Arterial calcification in diabetes mellitus: preclinical models and translational implications. Arterioscler Thromb Vasc Biol. 2017;37(2):205–17.PubMedCrossRef

64.

Terai K, Nara H, Takakura K, Mizukami K, Sanagi M, Fukushima S, et al. Vascular calcification and secondary hyperparathyroidism of severe chronic kidney disease and its relation to serum phosphate and calcium levels. Br J Pharmacol. 2009;156(8):1267–78.PubMedPubMedCentralCrossRef

65.

Li Z, Huang Y, Du J, Liu A, Tang C, Qi Y, et al. Endogenous sulfur dioxide inhibits vascular calcification in association with the TGF-β/Smad signaling pathway. Int J Mol Sci. 2016;17(3):266.PubMedPubMedCentralCrossRef

66.

Giachelli CM. The emerging role of phosphate in vascular calcification. Kidney Int. 2009;75(9):890–7.PubMedPubMedCentralCrossRef

67.

Cozzolino M, Dusso AS, Liapis H, Finch J, Lu Y, Burke SK, et al. The effects of sevelamer hydrochloride and calcium carbonate on kidney calcification in uremic rats. J Am Soc Nephrol. 2002;13(9):2299–308.PubMedCrossRef

68.

Lomashvili KA, Cobbs S, Hennigar RA, Hardcastle KI, O’Neill WC. Phosphate-induced vascular calcification: role of pyrophosphate and osteopontin. J Am Soc Nephrol. 2004;15(6):1392–401.PubMedCrossRef

69.

Mody N, Parhami F, Sarafian TA, Demer LL. Oxidative stress modulates osteoblastic differentiation of vascular and bone cells. Free Radic Biol Med. 2001;31(4):509–19.PubMedCrossRef

70.

Zhao MM, Xu MJ, Cai Y, Zhao G, Guan Y, Kong W, et al. Mitochondrial reactive oxygen species promote p65 nuclear translocation mediating high-phosphate-induced vascular calcification in vitro and in vivo. Kidney Int. 2011;79(10):1071–9.PubMedCrossRef

71.

Miller JD, Chu Y, Brooks RM, Richenbacher WE, Peña-Silva R, Heistad DD. Dysregulation of antioxidant mechanisms contributes to increased oxidative stress in calcific aortic valvular stenosis in humans. J Am Coll Cardiol. 2008;52(10):843–50.PubMedPubMedCentralCrossRef

72.

Hussain T, Tan B, Yin Y, Blachier F, Tossou MC, Rahu N. Oxidative stress and inflammation: what polyphenols can do for us? Oxidative Med Cell Longev. 2016;2016:7432797.CrossRef

73.

Tintut Y, Patel J, Parhami F, Demer LL. Tumor necrosis factor-alpha promotes in vitro calcification of vascular cells via the cAMP pathway. Circulation. 2000;102(21):2636–42.PubMedCrossRef

74.

Lencel P, Delplace S, Pilet P, Leterme D, Miellot F, Sourice S, et al. Cell-specific effects of TNF-α and IL-1β on alkaline phosphatase: implication for syndesmophyte formation and vascular calcification. Lab Investig. 2011;91(10):1434.PubMedCrossRef

75.

Awan Z, Denis M, Roubtsova A, Essalmani R, Marcinkiewicz J, Awan A, et al. Reducing vascular calcification by anti-IL-1β monoclonal antibody in a mouse model of familial hypercholesterolemia. Angiology. 2016;67(2):157–67.PubMedCrossRef

76.

Lin C-P, Huang P-H, Lai CF, Chen J-W, Lin S-J, Chen J-S. Simvastatin attenuates oxidative stress, NF-κB activation, and artery calcification in LDLR−/−mice fed with high fat diet via down-regulation of tumor necrosis factor-α and TNF receptor 1. PLoS One. 2015;10(12):e0143686.PubMedPubMedCentralCrossRef

77.

Han MS, Che X, Cho GH, Park HR, Lim KE, Park NR, et al. Functional cooperation between vitamin D receptor and Runx2 in vitamin D-induced vascular calcification. PLoS One. 2013;8(12):e83584.PubMedPubMedCentralCrossRef

78.

Yoshida T, Yamashita M, Hayashi M. Kruppel-like factor 4 contributes to high phosphate-induced phenotypic switching of vascular smooth muscle cells into osteogenic cells. J Biol Chem. 2012;287(31):25706–14.PubMedPubMedCentralCrossRef

79.

Hecht E, Freise C. Websky Kv, Nasser H, Kretzschmar N, Stawowy P, et al. the matrix metalloproteinases 2 and 9 initiate uraemic vascular calcifications. Nephrology Dialysis Transplantation. 2015;31(5):789–97.CrossRef

80.

Qin X, Corriere MA, Matrisian LM, Guzman RJ. Matrix metalloproteinase inhibition attenuates aortic calcification. Arterioscler Thromb Vasc Biol. 2006;26(7):1510–6.PubMedCrossRef

81.

Bäck M, Aranyi T, Cancela ML, Carracedo M, Conceição N, Leftheriotis G, et al. Endogenous calcification inhibitors in the prevention of vascular calcification: a consensus statement from the COST action EuroSoftCalcNet. Frontiers in cardiovascular medicine. 2018;5:196.PubMedCrossRef

82.

Scatena M, Liaw L, Giachelli CM. Osteopontin: a multifunctional molecule regulating chronic inflammation and vascular disease. Arterioscler Thromb Vasc Biol. 2007;27(11):2302–9.PubMedCrossRef

83.

Paloian NJ, Leaf EM, Giachelli CM. Osteopontin protects against high phosphate-induced nephrocalcinosis and vascular calcification. Kidney Int. 2016;89(5):1027–36.PubMedPubMedCentralCrossRef

84.

Wang F, Jiang T, Tang C, Su Z, Zhang N, Li G. Ghrelin reduces rat myocardial calcification induced by nicotine and vitamin D3 in vivo. Int J Mol Med. 2011;28(4):513–9.PubMed

85.

Zhang X, Li R, Qin X, Wang L, Xiao J, Song Y, et al. Sp1 plays an important role in vascular calcification both in vivo and in vitro. J Am Heart Assoc. 2018;7(6):e007555.PubMedPubMedCentralCrossRef

86.

Steitz SA, Speer MY, Curinga G, Yang HY, Haynes P, Aebersold R, et al. Smooth muscle cell phenotypic transition associated with calcification: upregulation of Cbfa1 and downregulation of smooth muscle lineage markers. Circ Res. 2001;89(12):1147–54.PubMedCrossRef

Titel: Flavocoxid Ameliorates Aortic Calcification Induced by Hypervitaminosis D3 and Nicotine in Rats Via Targeting TNF-α, IL-1β, iNOS, and Osteogenic Runx2
verfasst von: Ahmed E. Amer
George S. G. Shehatou
Hassan A. El-Kashef
Manar A. Nader
Ahmed R. El-Sheakh
Publikationsdatum: 26.07.2021
Verlag: Springer US
Erschienen in: Cardiovascular Drugs and Therapy / Ausgabe 6/2022
Print ISSN: 0920-3206
Elektronische ISSN: 1573-7241
DOI: https://doi.org/10.1007/s10557-021-07227-6

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