title: Inhibition of PARP prevents angiotensin II-induced aortic fibrosis in rats.
abstract: BACKGROUND
  Fibrosis is one of the major pathological features of hypertensive vascular disease. In this study, we aim to explore the possible protective effects of poly(ADP-ribose) polymerase (PARP) inhibitor on angiotensin II (AngII)-induced aortic fibrosis.
  
  
  METHODS
  Sprague-Dawley rats were infused subcutaneously with AngII. PARP inhibitor was intraperitoneally injected once a day. Collagen deposition in thoracic aorta was assayed by Masson tricrome staining. The mRNA and protein expression of TGF-β target genes involved in extracellular matrix (ECM) remodeling in aorta was measured. Plasma level and aortic expression of TGF-β1 was assayed. Correlation of systolic blood pressure (SBP) with plasma level of TGF-β1 was analyzed. In cultured rat vascular smooth muscle cells (VSMCs), effects of PARP inhibition on TGF-β1 expression, Smad3 transactivity, and TGF-β/Smad3 target gene expression were investigated.
  
  
  RESULTS
  Infusion of AngII promoted aortic PARP activation. Treatment with PARP inhibitor alleviated AngII-induced collagen deposition and expression of TGF-β target genes involved in ECM remodeling in aorta of rat. AngII increased plasma level and aortic expression of TGF-β1. A positive correlation between SBP and plasma level of TGF-β1 was revealed. Treatment with PARP inhibitor prevented AngII-induced elevation of SBP. Further experiments uncovered that AngII treatment increased TGF-β dependent gene expression through Smad3 pathway in cultured VSMCs. Inhibition of PARP prevented AngII-induced increases in TGF-β1 expression, Smad3 transactivity and its target gene expression.
  
  
  CONCLUSIONS
  These data indicate that inhibition of PARP prevents aortic fibrosis in AngII-induced hypertension in rats. This beneficial effect is mediated by inhibiting TGF-β/Smad3 pathway.
authors: Department of Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: Yan
authors: Y
authors: Wang
authors: Lin
authors: L
authors: Wang
authors: Fengxiao
authors: F
authors: Zhang
authors: Chun
authors: C
authors: Zhang
authors: Shan
authors: S
authors: Deng
authors: Rui
authors: R
authors: Wang
authors: Yun
authors: Y
authors: Zhang
authors: Dan
authors: D
authors: Huang
authors: Kai
authors: K
authors: Huang
mesh_terms: D000804:Angiotensin II / Q000633:toxicity*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D001549:Benzamides / Q000494:pharmacology / Q000627:therapeutic use; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005355:Fibrosis / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control; D008297:Male; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001549:Benzamides; D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D000804:Angiotensin II; C025160:3-aminobenzamide; D011065:Poly(ADP-ribose) Polymerases