title: Activation of peroxisome proliferator-activated receptor γ (PPARγ) through NF-κB/Brg1 and TGF-β1 pathways attenuates cardiac remodeling in pressure-overloaded rat hearts.
abstract: OBJECTIVE
  Cardiac remodeling is a common pathophysiological change along with chronic hypertension and myocardial infarction. Recent evidence indicated that cardiac tissue expressed peroxisome proliferator-activated receptor γ (PPARγ). However, the functional role of PPARγ in cardiac remodeling remained unclear. The present study was designed to investigate the relationship between PPARγ activation and pressure overload-induced cardiac remodeling.
  
  
  METHODS
  Cardiac remodeling model was successfully established by abdominal aorta ligation. Cardiac fibrosis and cardiomyocyte hypertrophy were simulated by 100 nM angiotensin II (Ang II) in vitro. Haemodynamic parameters, the expressions of Brg1, α-MHC, β-MHC, transforming growth factor beta 1 (TGF-β1), collagen-I, collagen-III and NF-κB were examined.
  
  
  RESULTS
  Morphological and haemodynamic measurements showed that the activation of PPARγ improved the impaired cardiac function and decreased interstitial fibrosis in cardiac remodeling rats. Further results also showed that the activation of PPARγ inhibited the expressions of Brg1 and TGF-β1 in the cardiac remodeling hearts. The activation of PPARγ also inhibited the proliferation and collagen production of cardiac fibroblasts, and down-regulated the activity of Brg1 and the expression of TGF-β1 induced by Ang II in cultured neonatal rat cardiomyocytes and cardiac fibroblasts, respectively, through NF-κB pathway.
  
  
  CONCLUSIONS
  These results suggested that PPARγ activation effectively inhibited cardiac remodeling processes by suppression of Brg1 and TGF-β1 expressions through NF-κB pathway in the pressure-overloaded hearts induced by abdominal aorta ligation in rats.
authors: Department of Pharmacology, Harbin Medical University-Daqing, Daqing, China.
authors: Han-Ping
authors: HP
authors: Qi
authors: Ye
authors: Y
authors: Wang
authors: Qian-Hui
authors: QH
authors: Zhang
authors: Jing
authors: J
authors: Guo
authors: Lei
authors: L
authors: Li
authors: Yong-Gang
authors: YG
authors: Cao
authors: Shu-Zhi
authors: SZ
authors: Li
authors: Xiao-Lei
authors: XL
authors: Li
authors: Mu-Mu
authors: MM
authors: Shi
authors: Wang
authors: W
authors: Xu
authors: Bai-Yan
authors: BY
authors: Li
authors: Hong-Li
authors: HL
authors: Sun
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D004265:DNA Helicases / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D011312:Pressure; D051381:Rats; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D020257:Ventricular Remodeling / Q000235:genetics
chemical_list: D016328:NF-kappa B; D009687:Nuclear Proteins; D047495:PPAR gamma; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D000804:Angiotensin II; C578929:Smarca4 protein, rat; D004265:DNA Helicases