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

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 alpha-smooth muscle actin) and inflammation (interleukin 1beta and tumor necrosis factor-alpha). 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-beta1 and overactivation of both transforming growth factor-beta/Smad and nuclear factor-kappaB 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 alpha-smooth muscle actin, as well as proinflammation cytokines (interleukin 1beta and tumor necrosis factor-alpha), 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-beta/Smad and nuclear factor-kappaB signaling pathways may be the mechanisms by which CRP promotes cardiac fibrosis and inflammation under high Ang II conditions.
AuthorsRongxin Zhang, Yuan Yuan Zhang, Xiao R Huang, Yin Wu, Arthur C K Chung, Ed Xuekui Wu, Alexander J Szalai, Benjamin C Y Wong, Chu-Pak Lau, Hui Y Lan
JournalHypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 55 Issue 4 Pg. 953-60 (Apr 2010) ISSN: 1524-4563 [Electronic] United States
PMID20157054 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Interleukin-1beta
  • Receptor, Angiotensin, Type 1
  • Smad Proteins
  • Tumor Necrosis Factor-alpha
  • Angiotensin II
  • C-Reactive Protein
Topics
  • Analysis of Variance
  • Angiotensin II (pharmacology)
  • Animals
  • Blood Pressure (drug effects, genetics)
  • C-Reactive Protein (genetics, metabolism)
  • Cells, Cultured
  • Enzyme-Linked Immunosorbent Assay
  • Fibrosis (metabolism, pathology)
  • Heart (drug effects, physiopathology)
  • Heart Rate (drug effects)
  • Humans
  • Hypertension (metabolism, pathology, physiopathology)
  • Immunohistochemistry
  • Inflammation (genetics, metabolism, pathology)
  • Interleukin-1beta (metabolism)
  • Mice
  • Myocardium (metabolism, pathology)
  • Receptor, Angiotensin, Type 1 (metabolism)
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Smad Proteins (metabolism)
  • Tumor Necrosis Factor-alpha (metabolism)
  • Up-Regulation
  • Ventricular Remodeling (genetics)

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