Inhibition of PARP prevents angiotensin II-induced aortic fibrosis in rats

Yan Wang, Lin Wang, Fengxiao Zhang, Chun Zhang, Shan Deng, Rui Wang, Yun Zhang, Dan Huang, Kai Huang

Research output: Contribution to journalArticle

19 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2285-2293
Number of pages9
JournalInternational Journal of Cardiology
Volume167
Issue number5
DOIs
StatePublished - Sep 1 2013

Keywords

  • Gene transcription
  • PARP
  • Smad
  • TGF-β
  • Vascular fibrosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Wang, Y., Wang, L., Zhang, F., Zhang, C., Deng, S., Wang, R., Zhang, Y., Huang, D., & Huang, K. (2013). Inhibition of PARP prevents angiotensin II-induced aortic fibrosis in rats. International Journal of Cardiology, 167(5), 2285-2293. https://doi.org/10.1016/j.ijcard.2012.06.050