C-reactive protein promotes cardiac fibrosis and inflammation in angiotensin II-induced hypertensive cardiac disease

Academic Article

Abstract

  • C-reactive protein (CRP) is a risk factor or biomarker for Cardiovascular diseases, including hypertension. The present study investigated the functional importance of human CRP in hypertensive Cardiac remodeling by a chronic infusion of angiotensin II (Ang II) into mice that express human CRP. Compared with the wild-type mice, although Ang II infusion Caused an equally high systolic blood pressure, levels of human CRP were further elevated, and Cardiac remodeling was markedly exacerbated in mice that express human CRP, resulting in a signifiCant reduction in the left ventricular ejection fraction and fractional shortening and an increase in Cardiac fibrosis (collagen I and III and α-smooth muscle actin) and inflammation (interleukin 1β and tumor necrosis factor-α). The enhancement in Cardiac remodeling in mice that express human CRP was associated with further upregulation of the Ang II type I receptor and transforming growth factor-β1 and overactivation of both transforming growth factor-β/Smad and nuclear factor-κB signaling pathways. Furthermore, in vitro studies in Cardiac fibroblasts revealed that CRP alone was able to signifiCantly induce expression of the Ang II type I receptor, collagen I/III, and α-smooth muscle actin, as well as proinflammation cytokines (interleukin 1β and tumor necrosis factor-α), which was further enhanced by addition of Ang II. In conclusion, CRP is not only a biomarker but also a mediator in Ang II-mediated Cardiac remodeling. Enhanced upregulation of the Ang II type I receptor and activation of the transforming growth factor-β/Smad and nuclear factor-κB signaling pathways may be the mechanisms by which CRP promotes Cardiac fibrosis and inflammation under high Ang II conditions. © 2010 American Heart Association, Inc.
  • Published In

  • Hypertension  Journal
  • Digital Object Identifier (doi)

    Author List

  • Zhang R; Zhang YY; Huang XR; Wu Y; Chung ACK; Wu EX; Szalai AJ; Wong BCY; Lau CP; Lan HY
  • Start Page

  • 953
  • End Page

  • 960
  • Volume

  • 55
  • Issue

  • 4