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Cardiovascular Diabetology
Published in: Cardiovascular Diabetology 1/2010

Open Access 01-12-2010 | Original investigation

Synergism in hyperhomocysteinemia and diabetes: role of PPAR gamma and tempol

Authors: Paras K Mishra, Neetu Tyagi, Utpal Sen, Irving G Joshua, Suresh C Tyagi

Published in: Cardiovascular Diabetology | Issue 1/2010

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Abstract

Background

Hyperhomocysteinemia (HHcy) and hyperglycemia cause diabetic cardiomyopathy by inducing oxidative stress and attenuating peroxisome proliferator- activated receptor (PPAR) gamma. However, their synergistic contribution is not clear.

Methods

Diabetic Akita (Ins2+/-) and hyperhomocysteinemic cystathionine beta synthase mutant (CBS+/-) were used for M-mode echocardiography at the age of four and twenty four weeks. The cardiac rings from WT, Akita and hybrid (Ins2+/-/CBS+/-) of Akita and CBS+/- were treated with different doses of acetylcholine (an endothelial dependent vasodilator). High performance liquid chromatography (HPLC) was performed for determining plasma homocysteine (Hcy) level in the above groups. Akita was treated with ciglitazone (CZ) - a PPAR gamma agonist and tempol-an anti-oxidant, separately and their effects on cardiac remodeling were assessed.

Results

At twenty four week, Akita mice were hyperglycemic and HHcy. They have increased end diastolic diameter (EDD). In their heart PPAR gamma, tissue inhibitor of metalloproteinase-4 (TIMP-4) and anti-oxidant thioredoxin were attenuated whereas matrix metalloproteinase (MMP)-9, TIMP-3 and NADPH oxidase 4 (NOX4) were induced. Interestingly, they showed synergism between HHcy and hyperglycemia for endothelial-myocyte (E-M) uncoupling. Additionally, treatment with CZ alleviated MMP-9 activity and fibrosis, and improved EDD. On the other hand, treatment with tempol reversed cardiac remodeling in part by restoring the expressions of TIMP-3,-4, thioredoxin and MMP-9.

Conclusions

Endogenous homocysteine exacerbates diabetic cardiomyopathy by attenuating PPAR gamma and inducing E-M uncoupling leading to diastolic dysfunction. PPAR gamma agonist and tempol mitigates oxidative stress and ameliorates diastolic dysfunction in diabetes.
Appendix
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Literature
1.
Ciaccio M, Bellia C: Hyperhomocysteinemia and cardiovascular risk: effect of vitamin supplementation in risk reduction. Curr Clin Pharmacol. 2010, 5: 30-36. 10.2174/157488410790410551.CrossRefPubMed
2.
Mendez-Gonzalez J, Rodriguez-Millan E, Julve J, Blanco-Vaca F: [Vitamin treatments that lower homocysteine concentration: can they decrease cerebrovascular disease in primary prevention?]. Rev Neurol. 2010, 50: 235-244.PubMed
3.
4.
Audelin MC, Genest J: Homocysteine and cardiovascular disease in diabetes mellitus. Atherosclerosis. 2001, 159: 497-511. 10.1016/S0021-9150(01)00531-7.CrossRefPubMed
5.
Dinavahi R, Falkner B: Relationship of homocysteine with cardiovascular disease and blood pressure. J Clin Hypertens (Greenwich). 2004, 6: 494-498. 10.1111/j.1524-6175.2004.03643.x.CrossRef
6.
Dominguez LJ, Galioto A, Pineo A, Ferlisi A, Ciaccio M, Putignano E, et al: Age, homocysteine, and oxidative stress: relation to hypertension and type 2 diabetes mellitus. J Am Coll Nutr. 2010, 29: 1-6.CrossRefPubMed
7.
Hoogeveen EK, Kostense PJ, Beks PJ, Mackaay AJ, Jakobs C, Bouter LM, et al: Hyperhomocysteinemia is associated with an increased risk of cardiovascular disease, especially in non-insulin-dependent diabetes mellitus: a population-based study. Arterioscler Thromb Vasc Biol. 1998, 18: 133-138.CrossRefPubMed
8.
Hoogeveen EK, Kostense PJ, Jakobs C, Dekker JM, Nijpels G, Heine RJ, et al: Hyperhomocysteinemia increases risk of death, especially in type 2 diabetes: 5-year follow-up of the Hoorn Study. Circulation. 2000, 101: 1506-1511.CrossRefPubMed
9.
Wald DS, Law M, Morris JK: Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ. 2002, 325: 1202-10.1136/bmj.325.7374.1202.PubMedCentralCrossRefPubMed
10.
Pavia C, Ferrer I, Valls C, Artuch R, Colome C, Vilaseca MA: Total homocysteine in patients with type 1 diabetes. Diabetes Care. 2000, 23: 84-87. 10.2337/diacare.23.1.84.CrossRefPubMed
11.
Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA. 2002, 288: 2015-2022. 10.1001/jama.288.16.2015.
12.
Carroll JF, Tyagi SC: Extracellular matrix remodeling in the heart of the homocysteinemic obese rabbit. Am J Hypertens. 2005, 18: 692-698. 10.1016/j.amjhyper.2004.11.035.CrossRefPubMed
13.
Singh AP, Singh M, Balakumar P: Effect of mast cell stabilizers in hyperhomocysteinemia-induced cardiac hypertrophy in rats. J Cardiovasc Pharmacol. 2008, 51: 596-604. 10.1097/FJC.0b013e31817ae60f.CrossRefPubMed
14.
Nosaka S, Murata K, Kobayashi M, Cheng ZB, Maruyama J: Inhibition of baroreflex vagal bradycardia by activation of the rostral ventrolateral medulla in rats. Am J Physiol Heart Circ Physiol. 2000, 279: H1239-H1247.PubMed
15.
Wang Y, Jones JF, Jeggo RD, de Burgh DM, Jordan D, Ramage AG: Effect of pulmonary C-fibre afferent stimulation on cardiac vagal neurones in the nucleus ambiguus in anaesthetized cats. J Physiol. 2000, 526 (Pt 1): 157-165. 10.1111/j.1469-7793.2000.t01-1-00157.x.PubMedCentralCrossRefPubMed
16.
Koz ST, Gouwy NT, Demir N, Nedzvetsky VS, Etem E, Baydas G: Effects of maternal hyperhomocysteinemia induced by methionine intake on oxidative stress and apoptosis in pup rat brain. Int J Dev Neurosci. 2010, 28: 325-329. 10.1016/j.ijdevneu.2010.02.006.CrossRefPubMed
17.
Sibrian-Vazquez M, Escobedo JO, Lim S, Samoei GK, Strongin RM: Homocystamides promote free-radical and oxidative damage to proteins. Proc Natl Acad Sci USA. 2010, 107: 551-554. 10.1073/pnas.0909737107.PubMedCentralCrossRefPubMed
18.
Solini A, Santini E, Nannipieri M, Ferrannini E: High glucose and homocysteine synergistically affect the metalloproteinases-tissue inhibitors of metalloproteinases pattern, but not TGFB expression, in human fibroblasts. Diabetologia. 2006, 49: 2499-2506. 10.1007/s00125-006-0377-2.CrossRefPubMed
19.
Solini A, Santini E, Ferrannini E: Effect of short-term folic acid supplementation on insulin sensitivity and inflammatory markers in overweight subjects. Int J Obes (Lond). 2006, 30: 1197-1202. 10.1038/sj.ijo.0803265.CrossRef
20.
Shastry S, Tyagi SC: Homocysteine induces metalloproteinase and shedding of beta-1 integrin in microvessel endothelial cells. J Cell Biochem. 2004, 93: 207-213. 10.1002/jcb.20137.CrossRefPubMed
21.
Rodriguez WE, Sen U, Tyagi N, Kumar M, Carneal G, Aggrawal D, et al: PPAR gamma agonist normalizes glomerular filtration rate, tissue levels of homocysteine, and attenuates endothelial-myocyte uncoupling in alloxan induced diabetic mice. Int J Biol Sci. 2008, 4: 236-244.PubMedCentralCrossRefPubMed
22.
Tyagi SC, Hoit BD: Metalloproteinase in myocardial adaptation and maladaptation. J Cardiovasc Pharmacol Ther. 2002, 7: 241-246. 10.1177/107424840200700407.CrossRefPubMed
23.
Fallon UB, Elwood P, Ben-Shlomo Y, Ubbink JB, Greenwood R, Smith GD: Homocysteine and ischaemic stroke in men: the Caerphilly study. J Epidemiol Community Health. 2001, 55: 91-96. 10.1136/jech.55.2.91.PubMedCentralCrossRefPubMed
24.
Fonseca VA, Fink LM, Kern PA: Insulin sensitivity and plasma homocysteine concentrations in non-diabetic obese and normal weight subjects. Atherosclerosis. 2003, 167: 105-109. 10.1016/S0021-9150(02)00386-6.CrossRefPubMed
25.
Basu R, Oudit GY, Wang X, Zhang L, Ussher JR, Lopaschuk GD, et al: Type 1 diabetic cardiomyopathy in the Akita (Ins2WT/C96Y) mouse model is characterized by lipotoxicity and diastolic dysfunction with preserved systolic function. Am J Physiol Heart Circ Physiol. 2009, 297: H2096-H2108. 10.1152/ajpheart.00452.2009.CrossRefPubMed
26.
Ishii I, Akahoshi N, Yamada H, Nakano S, Izumi T, Suematsu M: Cystathionine {gamma}-lyase-deficient mice require dietary cysteine to protect against acute lethal myopathy and oxidative injury. J Biol Chem. 2010, 20;285 (34): 26358-68. 10.1074/jbc.M110.147439. Epub 2010 Jun 21CrossRef
27.
Sen U, Munjal C, Qipshidze N, Abe O, Gargoum R, Tyagi SC: Hydrogen sulfide regulates homocysteine-mediated glomerulosclerosis. Am J Nephrol. 2010, 31: 442-455. 10.1159/000296717.PubMedCentralCrossRefPubMed
28.
Tyagi N, Mishra PK, Tyagi SC: Homocysteine, hydrogen sulfide (H2S) and NMDA-receptor in heart failure. Indian J Biochem Biophys. 2009, 46: 441-446.PubMed
29.
Tyagi N, Givvimani S, Qipshidze N, Kundu S, Kapoor S, Vacek JC, et al: Hydrogen sulfide mitigates matrix metalloproteinase-9 activity and neurovascular permeability in hyperhomocysteinemic mice. Neurochem Int. 2010, 56: 301-307. 10.1016/j.neuint.2009.11.002.PubMedCentralCrossRefPubMed
30.
Tenenbaum A, Fisman EZ, Motro M: Metabolic syndrome and type 2 diabetes mellitus: focus on peroxisome proliferator activated receptors (PPAR). Cardiovasc Diabetol. 2003, 2: 4-10.1186/1475-2840-2-4.PubMedCentralCrossRefPubMed
31.
Folmes CD, Clanachan AS, Lopaschuk GD: Fatty acid oxidation inhibitors in the management of chronic complications of atherosclerosis. Curr Atheroscler Rep. 2005, 7: 63-70. 10.1007/s11883-005-0077-2.CrossRefPubMed
32.
Nolte RT, Wisely GB, Westin S, Cobb JE, Lambert MH, Kurokawa R, et al: Ligand binding and co-activator assembly of the peroxisome proliferator-activated receptor-gamma. Nature. 1998, 395: 137-143. 10.1038/25931.CrossRefPubMed
33.
Itoh H, Doi K, Tanaka T, Fukunaga Y, Hosoda K, Inoue G, et al: Hypertension and insulin resistance: role of peroxisome proliferator-activated receptor gamma. Clin Exp Pharmacol Physiol. 1999, 26: 558-560. 10.1046/j.1440-1681.1999.03082.x.CrossRefPubMed
34.
Lebovitz HE, Banerji MA: Insulin resistance and its treatment by thiazolidinediones. Recent Prog Horm Res. 2001, 56: 265-294. 10.1210/rp.56.1.265.CrossRefPubMed
35.
Marx N, Sukhova G, Murphy C, Libby P, Plutzky J: Macrophages in human atheroma contain PPARgamma: differentiation-dependent peroxisomal proliferator-activated receptor gamma(PPARgamma) expression and reduction of MMP-9 activity through PPARgamma activation in mononuclear phagocytes in vitro. Am J Pathol. 1998, 153: 17-23.PubMedCentralCrossRefPubMed
36.
Bissonnette R, Treacy E, Rozen R, Boucher B, Cohn JS, Genest J: Fenofibrate raises plasma homocysteine levels in the fasted and fed states. Atherosclerosis. 2001, 155: 455-462. 10.1016/S0021-9150(00)00584-0.CrossRefPubMed
37.
Blane GF: Comparative toxicity and safety profile of fenofibrate and other fibric acid derivatives. Am J Med. 1987, 83: 26-36. 10.1016/0002-9343(87)90868-0.CrossRefPubMed
38.
Dierkes J, Westphal S, Luley C: Serum homocysteine increases after therapy with fenofibrate or bezafibrate. Lancet. 1999, 354: 219-220. 10.1016/S0140-6736(99)02153-4.CrossRefPubMed
39.
Brude IR, Finstad HS, Seljeflot I, Drevon CA, Solvoll K, Sandstad B, et al: Plasma homocysteine concentration related to diet, endothelial function and mononuclear cell gene expression among male hyperlipidaemic smokers. Eur J Clin Invest. 1999, 29: 100-108. 10.1046/j.1365-2362.1999.00419.x.CrossRefPubMed
40.
Barger PM, Brandt JM, Leone TC, Weinheimer CJ, Kelly DP: Deactivation of peroxisome proliferator-activated receptor-alpha during cardiac hypertrophic growth. J Clin Invest. 2000, 105: 1723-1730. 10.1172/JCI9056.PubMedCentralCrossRefPubMed
41.
Hunt MJ, Tyagi SC: Peroxisome proliferators compete and ameliorate Hcy-mediated endocardial endothelial cell activation. Am J Physiol Cell Physiol. 2002, 283: C1073-C1079.CrossRefPubMed
42.
Yamamoto K, Ohki R, Lee RT, Ikeda U, Shimada K: Peroxisome proliferator-activated receptor gamma activators inhibit cardiac hypertrophy in cardiac myocytes. Circulation. 2001, 104: 1670-1675. 10.1161/hc4001.097186.CrossRefPubMed
43.
Jagadeesha DK, Lindley TE, Deleon J, Sharma RV, Miller F, Bhalla RC: Tempol therapy attenuates medial smooth muscle cell apoptosis and neointima formation after balloon catheter injury in carotid artery of diabetic rats. Am J Physiol Heart Circ Physiol. 2005, 289: H1047-H1053. 10.1152/ajpheart.01071.2004.CrossRefPubMed
44.
Viswanad B, Srinivasan K, Kaul CL, Ramarao P: Effect of tempol on altered angiotensin II and acetylcholine-mediated vascular responses in thoracic aorta isolated from rats with insulin resistance. Pharmacol Res. 2006, 53: 209-215. 10.1016/j.phrs.2005.11.002.CrossRefPubMed
45.
Johansen JS, Harris AK, Rychly DJ, Ergul A: Oxidative stress and the use of antioxidants in diabetes: linking basic science to clinical practice. Cardiovasc Diabetol. 2005, 4: 5-10.1186/1475-2840-4-5.PubMedCentralCrossRefPubMed
46.
Watanabe M, Osada J, Aratani Y, Kluckman K, Reddick R, Malinow MR, et al: Mice deficient in cystathionine beta-synthase: animal models for mild and severe homocyst(e)inemia. Proc Natl Acad Sci USA. 1995, 92: 1585-1589. 10.1073/pnas.92.5.1585.PubMedCentralCrossRefPubMed
47.
Sivarajah A, McDonald MC, Thiemermann C: The cardioprotective effects of preconditioning with endotoxin, but not ischemia, are abolished by a peroxisome proliferator-activated receptor-gamma antagonist. J Pharmacol Exp Ther. 2005, 313: 896-901. 10.1124/jpet.104.080598.CrossRefPubMed
48.
Evans M, Anderson RA, Graham J, Ellis GR, Morris K, Davies S, et al: Ciprofibrate therapy improves endothelial function and reduces postprandial lipemia and oxidative stress in type 2 diabetes mellitus. Circulation. 2000, 101: 1773-1779.CrossRefPubMed
49.
Scatena R, Bottoni P, Giardina B: Mitochondria, PPARs, and Cancer: Is Receptor-Independent Action of PPAR Agonists a Key?. PPAR Res. 2008, 2008: 256251.PubMedCentralCrossRefPubMed
50.
Guo L, Zhang L, Sun Y, Muskhelishvili L, Blann E, Dial S, et al: Differences in hepatotoxicity and gene expression profiles by anti-diabetic PPAR gamma agonists on rat primary hepatocytes and human HepG2 cells. Mol Divers. 2006, 10: 349-360. 10.1007/s11030-006-9038-0.CrossRefPubMed
51.
Sen U, Tyagi N, Kumar M, Moshal KS, Rodriguez WE, Tyagi SC: Cystathionine-beta-synthase gene transfer and 3-deazaadenosine ameliorate inflammatory response in endothelial cells. Am J Physiol Cell Physiol. 2007, 293: C1779-C1787. 10.1152/ajpcell.00207.2007.CrossRefPubMed
52.
Tyagi SC, Smiley LM, Mujumdar VS: Homocyst(e)ine impairs endocardial endothelial function. Can J Physiol Pharmacol. 1999, 77: 950-957. 10.1139/cjpp-77-12-950.CrossRefPubMed
53.
Mishra PK, Tyagi N, Kundu S, Tyagi SC: MicroRNAs are involved in homocysteine-induced cardiac remodeling. Cell Biochem Biophys. 2009, 55: 153-162. 10.1007/s12013-009-9063-6.PubMedCentralCrossRefPubMed
54.
Garin I, Edghill EL, Akerman I, Rubio-Cabezas O, Rica I, Locke JM, et al: Recessive mutations in the INS gene result in neonatal diabetes through reduced insulin biosynthesis. Proc Natl Acad Sci USA. 2010, 107: 3105-3110. 10.1073/pnas.0910533107.PubMedCentralCrossRefPubMed
55.
Hong EG, Jung DY, Ko HJ, Zhang Z, Ma Z, Jun JY, et al: Nonobese, insulin-deficient Ins2Akita mice develop type 2 diabetes phenotypes including insulin resistance and cardiac remodeling. Am J Physiol Endocrinol Metab. 2007, 293: E1687-E1696. 10.1152/ajpendo.00256.2007.CrossRefPubMed
56.
Adamcova M, Potacova A, Popelova O, Sterba M, Mazurova Y, Aupperle H, et al: Cardiac remodeling and MMPs on the model of chronic daunorubicin-induced cardiomyopathy in rabbits. Physiol Res. 2010.
57.
Awad AE, Kandalam V, Chakrabarti S, Wang X, Penninger JM, Davidge ST, et al: Tumor necrosis factor induces matrix metalloproteinases in cardiomyocytes and cardiofibroblasts differentially via superoxide production in a PI3Kgamma-dependent manner. Am J Physiol Cell Physiol. 2010, 298: C679-C692. 10.1152/ajpcell.00351.2009.CrossRefPubMed
58.
Mishra PK, Tyagi N, Sen U, Givvimani S, Tyagi SC: H2 S ameliorates oxidative and proteolytic stresses and protects the heart against adverse remodeling in chronic heart failure. Am J Physiol Heart Circ Physiol. 2010, 298: H451-H456. 10.1152/ajpheart.00682.2009.PubMedCentralCrossRefPubMed
59.
Okada M, Yamawaki H, Hara Y: Angiotensin II enhances interleukin-1 beta-induced MMP-9 secretion in adult rat cardiac fibroblasts. J Vet Med Sci. 2010, 72: 735-739. 10.1292/jvms.09-0582.CrossRefPubMed
60.
Maheshwari A, Singh AK, Sinha DK, Tripathi K, Prakash J: Spectrum of renal disease in malaria. J Indian Med Assoc. 2004, 102: 143-146, 148PubMed
61.
Gonzalez A, Lopez B, Querejeta R, Zubillaga E, Echeverria T, Diez J: Filling pressures and collagen metabolism in hypertensive patients with heart failure and normal ejection fraction. Hypertension. 2010, 55: 1418-1424. 10.1161/HYPERTENSIONAHA.109.149112.CrossRefPubMed
62.
Gramley F, Lorenzen J, Knackstedt C, Rana OR, Saygili E, Frechen D, et al: Age-related atrial fibrosis. Age (Dordr). 2009, 31: 27-38. 10.1007/s11357-008-9077-9.CrossRef
63.
Johnson JL, Sala-Newby GB, Ismail Y, Aguilera CM, Newby AC: Low tissue inhibitor of metalloproteinases 3 and high matrix metalloproteinase 14 levels defines a subpopulation of highly invasive foam-cell macrophages. Arterioscler Thromb Vasc Biol. 2008, 28: 1647-1653. 10.1161/ATVBAHA.108.170548.PubMedCentralCrossRefPubMed
64.
Boaz M, Smetana S, Weinstein T, Matas Z, Gafter U, Iaina A, et al: Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): randomised placebo-controlled trial. Lancet. 2000, 356: 1213-1218. 10.1016/S0140-6736(00)02783-5.CrossRefPubMed
65.
Bell D, Zhao Y, McCoy FP, Devine AB, McDermott BJ: Differential effects of an anti-oxidant intervention on cardiomyocyte expression of adrenomedullin and intermedin and their receptor components in chronic nitric oxide deficiency. Cell Physiol Biochem. 2007, 20: 269-282. 10.1159/000107513.CrossRefPubMed
66.
Hahn SM, Mitchell JB, Shacter E: Tempol inhibits neutrophil and hydrogen peroxide-mediated DNA damage. Free Radic Biol Med. 1997, 23: 879-884. 10.1016/S0891-5849(97)00079-8.CrossRefPubMed
67.
Rippe C, Lesniewski L, Connell M, LaRocca T, Donato A, Seals D: Short-term calorie restriction reverses vascular endothelial dysfunction in old mice by increasing nitric oxide and reducing oxidative stress. Aging Cell. 2010, 9: 304-312. 10.1111/j.1474-9726.2010.00557.x.PubMedCentralCrossRefPubMed
68.
Zhang Y, Jang R, Mori TA, Croft KD, Schyvens CG, McKenzie KU, et al: The anti-oxidant Tempol reverses and partially prevents adrenocorticotrophic hormone-induced hypertension in the rat. J Hypertens. 2003, 21: 1513-1518. 10.1097/00004872-200308000-00015.CrossRefPubMed
Metadata
Title
Synergism in hyperhomocysteinemia and diabetes: role of PPAR gamma and tempol
Authors
Paras K Mishra
Neetu Tyagi
Utpal Sen
Irving G Joshua
Suresh C Tyagi
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2010
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/1475-2840-9-49

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