Angiotensin-receptor blockade reduces border zone myocardial monocyte chemoattractant protein-1 expression and macrophage infiltration in post-infarction ventricular remodeling

Takashi Kono, Toshihisa Anzai, Kotaro Naito, Yasuo Sugano, Yuichiro Maekawa, Toshiyuki Takahashi, Tsutomu Yoshikawa, Satoshi Ogawa

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Background: Monocyte chemoattractant protein-1 (MCP-1) is a key mediator of left ventricular (LV) remodeling during the early phase of myocardial infarction (MI). The hypothesis tested was that myocardial MCP-1 expression would increase during the chronic phase of MI and an angiotensin-II type 1 receptor blocker (ARB) would attenuate macrophage infiltration through decreased myocardial MCP-1 expression. Methods and Results: MI was produced by ligation of the left coronary artery in Wistar rats, which were then randomized to treatment with vehicle (MI/C), candesartan (10mg·kg -1·day-1) for 6 weeks (MI/ARB0-6W), or candesartan for 2 weeks, starting 4 weeks after MI (MI/ARB4-6W). LV systolic and end-diastolic pressures 6 weeks after MI were decreased in MI/ARB0-6W compared with MI/C or MI/ARB4-6W, however, there were no differences in other hemodynamic or echocardiographic parameters among infarcted rat groups. Both long-and short-term treatments with ARB similarly reduced mRNA expressions of MCP-1, transforming growth factor-β1, and procollagen type I and III, macrophage infiltration, and myocardial fibrosis in the border zone. Conclusions: In post-MI heart failure, ARB attenuated MCP-1 expression and macrophage infiltration in the border zone, resulting in less myocardial fibrosis. ARB may exert its beneficial effect, at least in part, by inhibiting myocardial macrophage-related inflammation.

Original languageEnglish
Pages (from-to)1685-1692
Number of pages8
JournalCirculation Journal
Volume72
Issue number10
DOIs
Publication statusPublished - 2008

Keywords

  • Chemokines
  • Fibrosis
  • Heart failure
  • Inflammation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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