Chronic treatment with an anti-ICAM-1 neutralizing antibody reduced macrophage accumulation, proliferative fibroblasts, TGF-beta expression, and prevented myocardial fibrosis in pressure-overloaded rats.
Does anti-ICAM-1 neutralizing antibody prevent macrophage accumulation and myocardial fibrosis in rats with pressure overload-induced cardiac remodeling?
ICAM-1 plays a crucial role in pressure overload-induced myocardial fibrosis by mediating macrophage accumulation and TGF-beta induction, highlighting a potential mechanism in hypertensive cardiac remodeling.
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.
Kuwahara et al. (Sat,) conducted a other in Hypertensive cardiac remodeling. Anti-ICAM-1 neutralizing antibody vs. Control IgG was evaluated on Macrophage accumulation, proliferative fibroblasts, TGF-beta expression, and myocardial fibrosis. Chronic treatment with an anti-ICAM-1 neutralizing antibody reduced macrophage accumulation, proliferative fibroblasts, TGF-beta expression, and prevented myocardial fibrosis in pressure-overloaded rats.