|Agonists at PPAR-gamma suppress angiotensin II-induced production of plasminogen activator inhibitor-1 and extracellular matrix in rat cardiac fibroblasts|
|Hao, G-H1,2; Niu, X-L1,2; Gao, D-F1; Wei, J.1; Wang, N-P3|
|关键词||PPAR-gamma angiotensin cardiac fibroblast plasminogen activator inhibitor-1 extracellular matrix rosiglitazone 15d-PGJ(2) fibrosis|
|刊名||BRITISH JOURNAL OF PHARMACOLOGY|
|WOS标题词||Science & Technology|
|类目[WOS]||Pharmacology & Pharmacy|
|研究领域[WOS]||Pharmacology & Pharmacy|
|关键词[WOS]||JUN NH2-TERMINAL KINASE ; RECEPTOR-GAMMA ; IN-VIVO ; VASCULAR FIBROSIS ; MYOCARDIAL-INFARCTION ; ENDOTHELIAL FUNCTION ; INCREASED EXPRESSION ; TYPE-1 EXPRESSION ; GENE-EXPRESSION ; STELLATE CELLS|
Background and purpose: Peroxisome proliferator-activated receptor (PPAR)-gamma ligands have been shown to inhibit cardiac fibrosis. However, the underlying mechanisms are poorly understood. We investigated the regulation by PPAR-gamma ligands of angiotensin (Ang) II-induced plasminogen activator inhibitor (PAI)-1, extracellular matrix (ECM) production and cell growth in cardiac fibroblasts.
Experimental approach: The effects of PPAR-gamma ligands on Ang II-induced PAI-1, ECM expression and cell growth were assessed in primary-cultured rat cardiac fibroblasts; cardiac PAI-1 and ECM production was examined in Ang II-infused rats.
Key results: In growth-arrested cardiac fibroblasts, PPAR-gamma ligands rosiglitazone and 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) dose-dependently attenuated Ang II-induced cell proliferation and expression of PAI-1, collagen type-I, collagen type-III and fibronectin. An accompanying increase in PPAR-gamma expression and activation was also observed. These suppressive effects were attenuated by the PPAR-gamma antagonists GW9662 and bisphenol A diglycidyl ether ( BADGE). Moreover, rosiglitazone and 15d-PGJ(2) inhibited in part the expression and phosphorylation of Ang II-induced transforming growth factor ( TGF)-beta 1, Smad2/3 and c-Jun NH(2)-terminal kinase (JNK). Ang II infusion in rats markedly increased left ventricular production of PAI-1, collagen and fibronectin, with a concurrent increase in the ratios of heart weight/body weight and left ventricle weight/body weight. Co-treatment with rosiglitazone significantly decreased these levels and upregulated PPAR-gamma expression.
Conclusions and implications: Rosiglitazone and 15d-PGJ2 suppress Ang II-induced production of PAI-1 and ECM probably via interactions between PPAR-gamma and TGF-beta 1/Smad2/3 and JNK signalling pathways. It is suggested that PPAR-gamma and its ligands may have potential applications in preventing cardiac fibrosis.
|作者单位||1.Xian Jiaotong Univ, Sch Med, Affiliated Hosp 2, Dept Cardiol, Xian 710004, Shaanxi, Peoples R China|
2.Xian Jiaotong Univ, Key Lab Environm & Genes Related Dis, Dept Cardiol, Minist Educ, Xian, Shaanxi, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Inst Cardiovasc Sci, Dept Cardiol, Beijing 100871, Peoples R China
|Hao, G-H,Niu, X-L,Gao, D-F,et al. Agonists at PPAR-gamma suppress angiotensin II-induced production of plasminogen activator inhibitor-1 and extracellular matrix in rat cardiac fibroblasts[J]. BRITISH JOURNAL OF PHARMACOLOGY,2008,153(7):1409-1419.|
|APA||Hao, G-H,Niu, X-L,Gao, D-F,Wei, J.,&Wang, N-P.(2008).Agonists at PPAR-gamma suppress angiotensin II-induced production of plasminogen activator inhibitor-1 and extracellular matrix in rat cardiac fibroblasts.BRITISH JOURNAL OF PHARMACOLOGY,153(7),1409-1419.|
|MLA||Hao, G-H,et al."Agonists at PPAR-gamma suppress angiotensin II-induced production of plasminogen activator inhibitor-1 and extracellular matrix in rat cardiac fibroblasts".BRITISH JOURNAL OF PHARMACOLOGY 153.7(2008):1409-1419.|