Roles of intercellular adhesion molecule-1 in hypertensive cardiac remodeling.

Abstract

Recently, we have shown that in rats with a suprarenal abdominal aortic constriction (AC), pressure overload induces early perivascular fibro-inflammatory changes (transforming growth factor [TGF]-beta induction and fibroblast proliferation) within the first week after AC and then causes the development of cardiac remodeling (myocyte hypertrophy and reactive myocardial fibrosis) associated with diastolic dysfunction. Intercellular adhesion molecule (ICAM)-1 is implicated in the recruitment of leukocytes, especially macrophages, in various inflammatory situations. Thus, we sought to investigate the causal relation of ICAM-1 to macrophage recruitment and cardiac remodeling in AC rats. In AC rats, immunoreactive ICAM-1 was observed transiently on endothelial cells of the intramyocardial coronary arterioles after day 1, with a peak at day 3, returning to baseline by day 7. Also, ED1+ macrophage accumulation was found in the area adjacent to the arteries expressing ICAM-1. Chronic treatment with an anti-ICAM-1 neutralizing antibody, but not with control IgG, remarkably reduced the accumulations of macrophages and proliferative fibroblasts and inhibited the upregulation of TGF-beta expression. Furthermore, the neutralizing antibody significantly prevented myocardial fibrosis without affecting arterial pressure and left ventricular and myocyte hypertrophy. In conclusion, ICAM-1 expression was induced by pressure overload in the intramyocardial arterioles, and triggered perivascular macrophage accumulation. In pressure-overloaded hearts, a crucial role in ICAM-1-mediated macrophage accumulation was suggested in the development of myocardial fibrosis, through TGF-beta induction and fibroblast activation.

• Authors: Fumitaka Kuwahara, Hisashi Kai, Keisuke Tokuda, Hiroshi Niiyama, Nobuhiro Tahara, Ken Kusaba, Kiyoko Takemiya, Ali Jalalidin, Mitsuhisa Koga, Tsuyoshi Nagata, Rei Shibata, Tsutomu Imaizumi
• Journal: Hypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 41 Issue 3 Pt 2 Pg. 819-23 (Mar 2003) ISSN: 1524-4563 [Electronic] United States
• PMID: 12624002 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Transforming Growth Factor beta
• Intercellular Adhesion Molecule-1

Topics

• Animals
• Antibodies, Monoclonal (pharmacology)
• Blood Pressure
• Cardiomegaly (etiology, metabolism, pathology)
• Cell Division
• Cell Movement
• Constriction
• Coronary Vessels (metabolism)
• Fibroblasts (physiology)
• Fibrosis
• Hypertension (metabolism, pathology, physiopathology)
• Inflammation (pathology)
• Intercellular Adhesion Molecule-1 (immunology, physiology)
• Macrophages (physiology)
• Male
• Myocytes, Cardiac (pathology)
• Pressure
• Rats
• Rats, Wistar
• Transforming Growth Factor beta (metabolism)