Peroxisome proliferator-activated receptor-γ is critical to cardiac fibrosis

PPAR Research

Volumn 2016, Issue , 2016, Pages

  Liu, Huang Jun ^a,b,c   Liao, Hai Han ^a,b,c   Yang, Zheng ^a,b,c   Tang, Qi Zhu ^a,b,c  

^a RENMIN HOSPITAL OF WUHAN UNIVERSITY   (China)

^b WUHAN UNIVERSITY   (China)

^c HUBEI KEY LABORATORY OF CARDIOLOGY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

2 CHLORO 5 NITRO N (4 PYRIDYL)BENZAMIDE; 2 CHLORO 5 NITROBENZANILIDE; CANDESARTAN; CIGLITAZONE; CURCUMIN; FELODIPINE; LOSARTAN; MESSENGER RNA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA 2; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA AGONIST; PIOGLITAZONE; ROSIGLITAZONE;

ATRIAL FIBRILLATION; CELL DIFFERENTIATION; CELL PROLIFERATION; DIABETES MELLITUS; DIABETIC CARDIOMYOPATHY; DISEASE ASSOCIATION; FIBROBLAST CULTURE; HEART FAILURE; HEART FIBROBLAST; HEART INFARCTION; HEART MUSCLE FIBROSIS; HUMAN; HYPERTENSION; NONHUMAN; PROTEIN FUNCTION; PROTEIN STRUCTURE; REPERFUSION INJURY; REVIEW;

EID: 84973441991     PISSN: 16874757     EISSN: 16874765     Source Type: Journal    
DOI: 10.1155/2016/2198645     Document Type: Review

References (106)

1. T. R. Cox and J. T. Erler, "Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer, " DiseaseModels and Mechanisms, vol. 4, no. 2, pp. 165-178, 2011.
2. A. Leask, "Potential therapeutic targets for cardiac fibrosis: TGFβ, angiotensin, endothelin, CCN2, and PDGF, partners in fibroblast activation, " Circulation Research, vol. 106, no. 11, pp. 1675-1680, 2010.
3. K. Nademanee, H. Raju, S. V. de Noronha et al., "Fibrosis, connexin-43, and conduction abnormalities in the Brugada syndrome, " Journal of the American College of Cardiology, vol. 66, no. 18, pp. 1976-1986, 2015.
4. J. E. Ho, C. Liu, A. Lyass et al., "Galectin-3, a marker of cardiac fibrosis, predicts incident heart failure in the community, " Journal of the American College of Cardiology, vol. 60, no. 14, pp. 1249-1256, 2012.
5. T. Ichiki, J. A. Schirger, B. K. Huntley et al., "Cardiac fibrosis in end-stage human heart failure and the cardiac natriuretic peptide guanylyl cyclase system: regulation and therapeutic implications, " Journal ofMolecular and Cellular Cardiology, vol. 75, pp. 199-205, 2014.
6. B. T. John, B. K. Tamarappoo, J. L. Titus, W. D. Edwards, W.-K. Shen, and S. S. Chugh, "Global remodeling of the ventricular interstitium in idiopathic myocardial fibrosis and sudden cardiac death, " Heart Rhythm, vol. 1, no. 2, pp. 141-149, 2004.
7. G. Krenning, E. M. Zeisberg, and R. Kalluri, "The origin of fibroblasts and mechanism of cardiac fibrosis, " Journal of Cellular Physiology, vol. 225, no. 3, pp. 631-637, 2010.
8. T. A. Wynn, "Cellular and molecular mechanisms of fibrosis, " The Journal of Pathology, vol. 214, no. 2, pp. 199-210, 2008.
9. Z.-Z. Zhang, Q.-H. Shang, H.-Y. Jin et al., "Cardiac protective effects of irbesartan via the PPAR-gamma signaling pathway in angiotensin-converting enzyme 2-deficient mice, " Journal of Translational Medicine, vol. 11, article 229, 2013.
10. Z. Meng, X.-H. Yu, J. Chen, L. Li, and S. Li, "Curcumin attenuates cardiac fibrosis in spontaneously hypertensive rats through PPAR-γ activation, " Acta Pharmacologica Sinica, vol. 35, no. 10, pp. 1247-1256, 2014.
11. K. Abou Daya, H. Abu Daya, M. Nasser Eddine, G. Nahhas, and N. Nuwayri-Salti, "Effects of rosiglitazone (PPARγ agonist) on the myocardium in non-hypertensive diabetic rats, " Journal of Diabetes, vol. 7, no. 1, pp. 85-94, 2015.
12. E. A. Ivanova, A. Parolari, V. Myasoedova, A. A. Melnichenko, Y. V. Bobryshev, and A. N. Orekhov, "Peroxisome proliferatoractivated receptor (PPAR) gamma in cardiovascular disorders and cardiovascular surgery, " Journal of Cardiology, vol. 66, no. 4, pp. 271-278, 2015.
13. S. Azhar, "Peroxisome proliferator-activated receptors, metabolic syndrome and cardiovascular disease, " Future Cardiology, vol. 6, no. 5, pp. 657-691, 2010.
14. W. S. Lee and J. Kim, "Peroxisome proliferator-activated receptors and the heart: lessons from the past and future directions, " PPAR Research, vol. 2015, Article ID 271983, 18 pages, 2015.
15. J. P. H. Wilding, "PPAR agonists for the treatment of cardiovascular disease in patients with diabetes, " Diabetes, Obesity and Metabolism, vol. 14, no. 11, pp. 973-982, 2012.
16. B. Grygiel-Gorniak, "Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications-a review, " Nutrition Journal, vol. 13, article 17, 2014.
17. D. Usud and T. Kanda, "Peroxisome proliferator-activated receptors for hypertension, " World Journal of Cardiology, vol. 6, no. 8, pp. 744-754, 2014.
18. I. Gurevich, A. M. Flores, and B. J. Aneskievich, "Corepressors of agonist-bound nuclear receptors, " Toxicology and Applied Pharmacology, vol. 223, no. 3, pp. 288-298, 2007.
19. L. Guo and R. Tabrizchi, "Peroxisome proliferator-activated receptor gamma as a drug target in the pathogenesis of insulin resistance, " Pharmacology and Therapeutics, vol. 111, no. 1, pp. 145-173, 2006.
20. C. Dong, H. Zhou, C. Shen et al., "Role of peroxisome proliferator-activated receptors gene polymorphisms in type 2 diabetes and metabolic syndrome, " World Journal of Diabetes, vol. 6, no. 4, pp. 654-661, 2015.
21. C. Christodoulides and A. Vidal-Puig, "PPARs and adipocyte function, " Molecular and Cellular Endocrinology, vol. 318, no. 1-2, pp. 61-68, 2010.
22. Y. Chen, A. R. Jimenez, and J. D. Medh, "Identification and regulation of novel PPAR-γ splice variants in human THP macrophages " Biochimica et Biophysica Acta (BBA)-Gene Structure and Expression, vol. 1759, no. 1-2, pp. 32-43, 2006.
23. G. Medina-Gomez, S. L. Gray, L. Yetukuri et al., "PPARgamma2 prevents lipotoxicity by controlling adipose tissue expandability and peripheral lipid metabolism, " PLoS genetics, vol. 3, no. 4, article e64, 2007.
24. P. A. Sarafidis and A. N. Lasaridis, "Actions of peroxisome proliferator-activated receptors-γ agonists explaining a possible blood pressure-lowering effect, " American Journal of Hypertension, vol. 19, no. 6, pp. 646-653, 2006.
25. M. Iglarz, R. M. Touyz, E. C. Viel et al., "Peroxisome proliferator-activated receptor-α and receptor-γ activators prevent cardiac fibrosis in mineralocorticoid-dependent hypertension, " Hypertension, vol. 42, no. 4, pp. 737-743, 2003.
26. S. Lim, K.-S. Lee, J. E. Lee et al., "Effect of a new PPARgamma agonist, lobeglitazone, on neointimal formation after balloon injury in rats and the development of atherosclerosis, " Atherosclerosis, vol. 243, no. 1, Article ID14251, pp. 107-119, 2015.
27. I. Wojtkowska, A. Tysarowski, K. Seliga et al., "PPAR gamma expression levels during development of heart failure in patients with coronary artery disease after coronary artery bypassgrafting, " PPAR Research, vol. 2014, Article ID 242790, 5 pages, 2014.
28. H. E. Mohamad, M. E. Askar, and M. M. Hafez, "Management of cardiac fibrosis in diabetic rats: the role of peroxisome proliferator activated receptor gamma (PPAR-gamma) and calcium channel blockers (CCBs), " Diabetology and Metabolic Syndrome, vol. 3, no. 1, article 4, 2011.
29. H. Zhang, T. Wei, X. Jiang et al., "PEDF and 34-mer inhibit angiogenesis in the heart by inducing tip cells apoptosis via upregulating PPAR-γ to increase surface FasL, " Apoptosis, vol. 21, no. 1, pp. 60-68, 2016.
30. Y. Chu, D. D. Lund, R. M. Weiss et al., "Pioglitazone attenuates valvular calcification induced by hypercholesterolemia, " Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 33, no. 3, pp. 523-532, 2013.
31. T. Motoki, H. Kurobe, Y. Hirata et al., "PPAR-γ agonist attenuates inflammation in aortic aneurysm patients, " General Thoracic and Cardiovascular Surgery, vol. 63, no. 10, pp. 565-571, 2015.
32. S. Lim, J. J. Cheng, M. Kim et al., "PPARγ gene transfer sustains apoptosis, inhibits vascular smooth muscle cell proliferation, and reduces neointima formation after balloon injury in rats, " Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 26, no. 4, pp. 808-813, 2006.
33. Q. Hu, J. Chen, C. Jiang, and H.-F. Liu, "Effect of peroxisome proliferator-activated receptor gamma agonist on heart of rabbits with acute myocardial ischemia/reperfusion injury, " Asian Pacific Journal of Tropical Medicine, vol. 7, no. 4, pp. 271-275, 2014.
34. H. Wang, Q. W. Zhu, P. Ye et al., "Pioglitazone attenuates myocardial ischemia-reperfusion injury via up-regulation of ERK and COX-2, " BioScience Trends, vol. 6, no. 6, pp. 325-332, 2012.
35. S.-H. Ihm, K. Chang, H.-Y. Kimet al., "Peroxisome proliferatoractivated receptor-γ activation attenuates cardiac fibrosis in type 2 diabetic rats: the effect of rosiglitazone on myocardial expression of receptor for advanced glycation end products and of connective tissue growth factor, " Basic Research inCardiology, vol. 105, no. 3, pp. 399-407, 2010.
36. S. M. Zhao, "Cardiac fibrosis in diabetic rats: regulation and mechanism of activation of the PPARγ signal pathway, " The Chinese Journal of Physiology, vol. 53, no. 4, pp. 262-267, 2010.
37. T. da Silva Torres, M. B. Aguila, and C. A. Mandarim-de- Lacerda, "Rosiglitazone reverses cardiac adverse remodeling (fibrosis and vascularization) in perinatal low protein rat offspring, " Pathology Research and Practice, vol. 206, no. 9, pp. 642-646, 2010.
38. T. Liu, H. Zhao, J. Li, P. Korantzopoulos, and G. Li, "Rosiglitazone attenuates atrial structural remodeling and atrial fibrillation promotion in alloxan-induced diabetic rabbits, " CardiovascularTherapeutics, vol. 32, no. 4, pp. 178-183, 2014.
39. N. Makino, M. Sasaki, T. Maeda, and K. Mimori, "Telomere biology in cardiovascular disease-role of insulin sensitivity in diabetic hearts, " Experimental and Clinical Cardiology, vol. 15, no. 4, pp. e128-e133, 2010.
40. P. K. Mishra, N. Tyagi, U. Sen, I. G. Joshua, and S. C. Tyagi, "Synergism in hyperhomocysteinemia and diabetes: role of PPAR gamma and tempol, " Cardiovascular Diabetology, vol. 9, article 49, 2010.
41. C. Y. Shim, B.-W. Song, M.-J. Cha et al., "Combination of a peroxisome proliferator-activated receptor-gamma agonist and an angiotensin II receptor blocker attenuates myocardial fibrosis and dysfunction in type 2 diabetic rats, " Journal of Diabetes Investigation, vol. 5, no. 4, pp. 362-371, 2014.
42. K. Gong, Y.-F. Chen, P. Li et al., "Transforming growth factor- βinhibits myocardial PPARγ expression in pressure overloadinduced cardiac fibrosis and remodeling in mice, " Journal of Hypertension, vol. 29, no. 9, pp. 1810-1819, 2011.
43. H.-P. Qi, Y. Wang, Q.-H. Zhang et al., "Activation of peroxisome proliferator-activated receptor γ (PPARγ) through NF- κB/brg1 and TGF-β1 pathways attenuates cardiac remodeling in pressure-overloaded rat hearts, " Cellular Physiology and Biochemistry, vol. 35, no. 3, pp. 899-912, 2015.
44. T. Shinzato, Y. Ohya, M. Nakamoto, A. Ishida, and S. Takishita, "Beneficial effects of pioglitazone on left ventricular hypertrophy in genetically hypertensive rats, " Hypertension Research, vol. 30, no. 9, pp. 863-873, 2007.
45. Q. N. Diep, F. Amiri, K. Benkirane, P. Paradis, and E. L. Schiffrin, "Long-term effects of the PPARγ activator pioglitazone on cardiac inflammation in stroke-prone spontaneously hypertensive rats, " Canadian Journal of Physiology and Pharmacology, vol. 82, no. 11, pp. 976-985, 2004.
46. T. Nakamura, E. Yamamoto, K. Kataoka et al., "Beneficial effects of pioglitazone on hypertensive cardiovascular injury are enhanced by combination with candesartan, " Hypertension, vol. 51, no. 2, pp. 296-301, 2008.
47. B. C. Henderson, U. Sen, C. Reynolds et al., "Reversal of systemic hypertension-associated cardiac remodeling in chronic pressure overload myocardium by ciglitazone, " International Journal of Biological Sciences, vol. 3, no. 6, pp. 385-392, 2007.
48. M. F. Kato, R. Shibata, K. Obata et al., "Pioglitazone attenuates cardiac hypertrophy in rats with salt-sensitive hypertension: role of activation of AMP-activated protein kinase and inhibition of Akt, " Journal of Hypertension, vol. 26, no. 8, pp. 1669-1676, 2008.
49. S. Gray and J. K. Kim, "New insights into insulin resistance in the diabetic heart, " Trends in Endocrinology and Metabolism, vol. 22, no. 10, pp. 394-403, 2011.
50. R. Candido, J. M. Forbes, M. C. Thomas et al., "A breaker of advanced glycation end products attenuates diabetes-induced myocardial structural changes, " Circulation Research, vol. 92, no. 7, pp. 785-792, 2003.
51. N. Koitabashi, M. Arai, S. Kogure et al., "Increased connective tissue growth factor relative to brain natriuretic peptide as a determinant of myocardial fibrosis, " Hypertension, vol. 49, no. 5, pp. 1120-1127, 2007.
52. C. H. Mandavia, A. R. Aroor, V. G. Demarco, and J. R. Sowers, "Molecular and metabolic mechanisms of cardiac dysfunction in diabetes, " Life Sciences, vol. 92, no. 11, pp. 601-608, 2013.
53. M. T. Quintana, J. He, J. Sullivan et al., "Muscle ring finger-3 protects against diabetic cardiomyopathy induced by a high fat diet, " BMC Endocrine Disorders, vol. 15, no. 1, article 36, 2015.
54. J. He, M. T. Quintana, J. Sullivan et al., "MuRF2 regulates PPARγ1 activity to protect against diabetic cardiomyopathy and enhance weight gain induced by a high fat diet, " Cardiovascular Diabetology, vol. 14, article 97, 2015.
55. H. Zhao, D. W. Gu, H. T. Li, Q. F. Ge, and G. P. Li, "Inhibitory effects of spironolactone on myocardial fibrosis in spontaneously hypertensive rats, "Genetics andMolecular Research, vol. 14, no. 3, pp. 10315-10321, 2015.
56. S. Zambrano, A. J. Blanca, M. V. Ruiz-Armenta et al., "LCarnitine protects against arterial hypertension-related cardiac fibrosis through modulation of PPAR-γ expression, " Biochemical Pharmacology, vol. 85, no. 7, pp. 937-944, 2013.
57. A. Kis, C. Murdoch, M. Zhang et al., "Defective peroxisomal proliferators activated receptor gamma activity due to dominant-negative mutation synergizes with hypertension to accelerate cardiac fibrosis in mice, " European Journal of Heart Failure, vol. 11, no. 6, pp. 533-541, 2009.
58. Y. Maejima, H. Okada, G. Haraguchi et al., "Telmisartan, a unique ARB, improves left ventricular remodeling of infarcted heart by activating PPAR gamma, " Laboratory Investigation, vol. 91, no. 6, pp. 932-944, 2011.
59. D. Fliegner, D. Westermann, A. Riad et al., "Up-regulation of PPARγ in myocardial infarction, " European Journal of Heart Failure, vol. 10, no. 1, pp. 30-38, 2008.
60. M. Schupp, J. Janke, R. Clasen, T. Unger, and U. Kintscher, "Angiotensin type 1 receptor blockers induce peroxisome proliferator-activated receptor-γ activity, " Circulation, vol. 109, no. 17, pp. 2054-2057, 2004.
61. T. Shiomi, H. Tsutsui, S. Hayashidani et al., "Pioglitazone, a peroxisome proliferator-activated receptor-γ agonist, attenuates left ventricular remodeling and failure after experimental myocardial infarction, " Circulation, vol. 106, no. 24, pp. 3126-3132, 2002.
62. L. Tao, S. Shen, S. Fu et al., "Traditional Chinese Medication Qiliqiangxin attenuates cardiac remodeling after acute myocardial infarction in mice, " Scientific Reports, vol. 5, article 8374, 10 pages, 2015.
63. Y. Birnbaum, B. Long, J. Qian, J. R. Perez-Polo, and Y. Ye, "Pioglitazone limits myocardial infarct size, activates Akt, and upregulates cPLA2 and COX-2 in a PPAR-γ-independent manner, " Basic Research in Cardiology, vol. 106, no. 3, pp. 431-446, 2011.
64. S. Frantz, K. Hu, J. Widder et al., "Peroxisome proliferator activated-receptor agonism and left ventricular remodeling in mice with chronic myocardial infarction, " British Journal of Pharmacology, vol. 141, no. 1, pp. 9-14, 2004.
65. C. A. Lygate, K. Hulbert, M. Monfared, M. A. Cole, K. Clarke, and S. Neubauer, "The PPARγ-activator rosiglitazone does not alter remodeling but increasesmortality in rats post-myocardial infarction, " Cardiovascular Research, vol. 58, no. 3, pp. 632-637, 2003.
66. S. Sarma, "Use of clinically available PPAR agonists for heart failure; do the risks outweigh the potential benefits?" Current Molecular Pharmacology, vol. 5, no. 2, pp. 255-263, 2012.
67. C. Zou, H. Qi, Z.-H. Liu, L. Han, C. Zhao, and X. Yang, "Simvastatin activates the PPARγ-dependent pathway to prevent left ventricular hypertrophy associated with inhibition of RhoA signaling, " Texas Heart Institute Journal, vol. 40, no. 2, pp. 140-147, 2013.
68. M. Shimano, Y. Tsuji, Y. Inden et al., "Pioglitazone, a peroxisome proliferator-activated receptor-gamma activator, attenuates atrial fibrosis and atrial fibrillation promotion in rabbits with congestive heart failure, " Heart Rhythm, vol. 5, no. 3, pp. 451-459, 2008.
69. D. Gomez-Garre, M. Herraiz, M. L. Gonzalez-Rubio et al., "Activation of peroxisome proliferator-activated receptor-α and -γ in auricular tissue from heart failure patients, " European Journal of Heart Failure, vol. 8, no. 2, pp. 154-161, 2006.
70. X. Wang, X. Liu, Y. Zhan et al., "Pharmacogenomic, physiological, and biochemical investigations on safety and efficacy biomarkers associated with the peroxisome proliferatoractivated receptor-γ activator rosiglitazone in rodents: a translationalmedicine investigation, "TheJournal of Pharmacology and Experimental Therapeutics, vol. 334, no. 3, pp. 820-829, 2010.
71. A. Prasad, G. W. Stone, D. R. Holmes, and B. Gersh, "Reperfusion injury, microvascular dysfunction, and cardioprotection: the dark side' of reperfusion, " Circulation, vol. 120, no. 21, pp. 2105-2112, 2009.
72. S.-W. Lee, J.-Y. Won, H.-Y. Lee et al., "Angiopoietin-1 protects heart against ischemia/reperfusion injury throughVE-cadherin dephosphorylation andmyocardiac integrin-β1/ERK/caspase-9 phosphorylation cascade, " Molecular Medicine, vol. 17, no. 9-10, pp. 1095-1106, 2011.
73. N. Khandoudi, P. Delerive, I. Berrebi-Bertrand, R. E. Buckingham, B. Staels, and A. Bril, "Rosiglitazone, a peroxisome proliferator-activated receptor-γ, inhibits the JunNH2-terminal kinase/activating protein 1 pathway and protects the heart from ischemia/reperfusion injury, " Diabetes, vol. 51, no. 5, pp. 1507-1514, 2002.
74. D. Nagarajan, T. Melo, Z. Deng, C. Almeida, and W. Zhao, "ERK/GSK3β/Snail signaling mediates radiation-induced alveolar epithelial-to-mesenchymal transition, " Free Radical Biology and Medicine, vol. 52, no. 6, pp. 983-992, 2012.
75. R. G. Rowe, Y. Lin, R. Shimizu-Hirota et al., "Hepatocytederived snail1 propagates liver fibrosis progression, " Molecular and Cellular Biology, vol. 31, no. 12, pp. 2392-2403, 2011.
76. A. Boutet, M. A. Esteban, P. H. Maxwell, and M. A. Nieto, "Reactivation of Snail genes in renal fibrosis and carcinomas: a process of reversed embryogenesis?" Cell Cycle, vol. 6, no. 6, pp. 638-642, 2007.
77. S.-W. Lee, J.-Y. Won, W. J. Kim et al., "Snail as a potential target molecule in cardiac fibrosis: paracrine action of endothelial cells on fibroblasts through snail and CTGF Axis, " Molecular Therapy, vol. 21, no. 9, pp. 1767-1777, 2013.
78. S. P. J. Krul, W. R. Berger, N. W. Smit et al., "Response to letter regarding article, atrial fibrosis and conduction slowing in the left atrial appendage of patients undergoing thoracoscopic surgical pulmonary vein isolation for atrial fibrillation', " Circulation: Arrhythmia and Electrophysiology, vol. 8, no. 4, p. 997, 2015.
79. B. Burstein and S. Nattel, "Atrial fibrosis: mechanisms and clinical relevance in atrial fibrillation, " Journal of the American College of Cardiology, vol. 51, no. 8, pp. 802-809, 2008.
80. X. Chen, Z. Bing, J. He et al., "Downregulation of peroxisome proliferator-activated receptor-γ expression in hypertensive atrial fibrillation, " Clinical Cardiology, vol. 32, no. 6, pp. 337-345, 2009.
81. Q. Lin, L. Jia, and Y. Sun, "A pilot study of circulating PPAR- γ receptor protein in elderly patients with atrial fibrillation, " Archives of Medical Science, vol. 8, no. 3, pp. 471-476, 2012.
82. J. Gu, X. Liu, Q.-X. Wang et al., "Beneficial effects of pioglitazone on atrial structural and electrical remodeling in vitro cellular models, " Journal of Molecular and Cellular Cardiology, vol. 65, pp. 1-8, 2013.
83. M. Chello, P. Mastroroberto, R. Romano, S. Zofrea, I. Bevacqua, and A. R. Marchese, "Changes in the proportion of types I and III collagen in the left ventricular wall of patients with postirradiative pericarditis, " Cardiovascular Surgery, vol. 4, no. 2, pp. 222-226, 1996.
84. S. Gao, R. Wu, and Y. Zeng, "Up-regulation of peroxisome proliferator-activated receptor gamma in radiation-induced heart injury in rats, " Radiation and Environmental Biophysics, vol. 51, no. 1, pp. 53-59, 2012.
85. L. Jing, L.-J. Zhou, F.-M. Zhang, W.-M. Li, and Y. Sang, "Tenascin-x facilitates myocardial fibrosis and cardiac remodeling through transforming growth factor-β1 and peroxisome proliferatoractivated receptor β in alcoholic cardiomyopathy, " Chinese Medical Journal, vol. 124, no. 3, pp. 390-395, 2011.
86. H. Hasegawa, H. Takano, Y. Zou et al., "Pioglitazone, a peroxisome proliferator-activated receptor γ activator, ameliorates experimental autoimmune myocarditis by modulating Th1/Th2 balance, " Journal of Molecular and Cellular Cardiology, vol. 38, no. 2, pp. 257-265, 2005.
87. A. P. Singh, T. Kaur, R. S. Dahiya, N. Singh, and P. M. Singh Bedi, "Ameliorative role of rosiglitazone in hyperhomocysteinemiainduced experimental cardiac hypertrophy, " Journal of Cardiovascular Pharmacology, vol. 56, no. 1, pp. 53-59, 2010.
88. Y.-W. Qin, P. Ye, J.-Q. He, L. Sheng, L.-Y. Wang, and J. Du, "Simvastatin inhibited cardiac hypertrophy and fibrosis in apolipoprotein E-deficient mice fed a Western-style diet' by increasing PPAR α and γ expression and reducing TC, MMP-9, and Cat S levels, " Acta Pharmacologica Sinica, vol. 31, no. 10, pp. 1350-1358, 2010.
89. N. Rani, S. Bharti, J. Bhatia et al., "Inhibition of TGF-β by a novel PPAR-γ agonist, chrysin, salvages β-receptor stimulated myocardial injury in rats through MAPKs-dependent mechanism, " Nutrition and Metabolism, vol. 12, article 11, 2015.
90. R. Chen, J. Xue, and M. Xie, "Puerarin prevents isoprenalineinducedmyocardial fibrosis in mice by reduction ofmyocardial TGF-β1 expression, " The Journal of Nutritional Biochemistry, vol. 23, no. 9, pp. 1080-1085, 2012.
91. R. Chen, J. Xue, and M.-L. Xie, "Reduction of isoprenalineinduced myocardial TGF-β1 expression and fibrosis in ostholetreated mice, " Toxicology and Applied Pharmacology, vol. 256, no. 2, pp. 168-173, 2011.
92. B.-Y. Guo, Y.-J. Li, R. Han et al., "Telmisartan attenuates isoproterenol-induced cardiac remodeling in rats via regulation of cardiac adiponectin expression, " Acta Pharmacologica Sinica, vol. 32, no. 4, pp. 449-455, 2011.
93. K. E. Porter and N. A. Turner, "Cardiac fibroblasts: at the heart of myocardial remodeling, " Pharmacology and Therapeutics, vol. 123, no. 2, pp. 255-278, 2009.
94. R. D. Brown, S. K. Ambler, M. D. Mitchell, and C. S. Long, "The cardiac fibroblast: therapeutic target in myocardial remodeling and failure, " Annual Review of Pharmacology and Toxicology, vol. 45, pp. 657-687, 2005.
95. G.-H. Hao, X.-L. Niu, D.-F. Gao, J. Wei, and N.-P. Wang, "Agonists at PPAR-γ suppress angiotensin II-induced production of plasminogen activator inhibitor-1 and extracellular matrix in rat cardiac fibroblasts, " British Journal of Pharmacology, vol. 153, no. 7, pp. 1409-1419, 2008.
96. X. Hou, Y. Zhang, Y. H. Shen et al., "PPAR-γ activation by rosiglitazone suppresses angiotensin II-mediated proliferation and phenotypictransition in cardiac fibroblasts via inhibition of activation of activator protein 1, " European Journal of Pharmacology, vol. 715, no. 1-3, pp. 196-203, 2013.
97. S.-M. Zhao, L.-H. Shen, H.-W. Li et al., "Down-regulation of the expression of angiotensin II type 1 receptor in neonatal rat cardiac fibroblast by activation of PPARγ signal pathway, " Chinese Journal of Physiology, vol. 51, no. 6, pp. 357-362, 2008.
98. J. Li, N. F. Liu, and Q. Wei, "Effect of rosiglitazone on cardiac fibroblast proliferation, nitric oxide production and connective tissue growth factor expression induced by advanced glycation end-products, " Journal of International Medical Research, vol. 36, no. 2, pp. 329-335, 2008.
99. R. Martin, M. Miana, R. Jurado-Lopez et al., "Diol triterpenes block profibrotic effects of angiotensin II and protect from cardiac hypertrophy, " PLoS ONE, vol. 7, no. 7, Article ID e41545, 2012.
100. E. M. Seymour, M. R. Bennink, S. W. Watts, and S. F. Bolling, "Whole grape intake impacts cardiac peroxisome proliferatoractivated receptor and nuclear factor κb activity and cytokine expression in rats with diastolic dysfunction, " Hypertension, vol. 55, no. 5, pp. 1179-1185, 2010.
101. R. Chen, J. Xue, and M. Xie, "Osthole regulates TGF-β1 and MMP-2/9 expressions via activation of PPARα/γ in cultured mouse cardiac fibroblasts stimulated with angiotensin II, " Journal of Pharmacy and Pharmaceutical Sciences, vol. 16, no. 5, pp. 732-741, 2013.
102. S. E. Nissen and K. Wolski, "Effect of rosiglitazone on the risk ofmyocardial infarction and death fromcardiovascular causes, " The New England Journal ofMedicine, vol. 356, no. 24, pp. 2457-2471, 2007.
103. R. W. Nesto, D. Bell, R. O. Bonow et al., "Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association, " Diabetes Care, vol. 27, no. 1, pp. 256-263, 2004.
104. T. Hampton, "Diabetes drugs tied to fractures in women, " The Journal of the American Medical Association, vol. 297, no. 15, p. 1645, 2007.
105. A. M. Lincoff, J.-C. Tardif, G. G. Schwartz et al., "Effect of aleglitazar on cardiovascular outcomes after acute coronary syndrome in patients with type 2 diabetes mellitus: the Ale- Cardio randomized clinical trial, " The Journal of the American Medical Association, vol. 311, no. 15, pp. 1515-1525, 2014.
106. R. Chen, F. Liang, J. Moriya et al., "Peroxisome proliferatoractivated receptors (PPARs) and their agonists for hypertension and heart failure: are the reagents beneficial or harmful?" International Journal of Cardiology, vol. 130, no. 2, pp. 131-139, 2008.