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

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 (10 mg.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-beta1, 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.

• Authors: Takashi Kohno, Toshihisa Anzai, Kotaro Naito, Yasuo Sugano, Yuichiro Maekawa, Toshiyuki Takahashi, Tsutomu Yoshikawa, Satoshi Ogawa
• Journal: Circulation journal : official journal of the Japanese Circulation Society (Circ J) Vol. 72 Issue 10 Pg. 1685-92 (Oct 2008) ISSN: 1346-9843 [Print] Japan
• PMID: 18753699 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Angiotensin Receptor Antagonists
• Benzimidazoles
• Biphenyl Compounds
• Ccl2 protein, rat
• Chemokine CCL2
• DNA Primers
• RNA, Messenger
• Tetrazoles
• RNA
• Collagen
• candesartan

Topics

• Angiotensin II Type 1 Receptor Blockers (therapeutic use)
• Angiotensin Receptor Antagonists
• Animals
• Benzimidazoles (therapeutic use)
• Biphenyl Compounds
• Chemokine CCL2 (genetics)
• Collagen (metabolism)
• DNA Primers
• Disease Models, Animal
• Male
• Myocardial Infarction (pathology, prevention & control)
• RNA (genetics)
• RNA, Messenger (genetics)
• Rats
• Rats, Wistar
• Reverse Transcriptase Polymerase Chain Reaction
• Tetrazoles (therapeutic use)
• Ventricular Remodeling (drug effects, physiology)