Cardiac remodeling: Role of neovascularization in heart failure

Abstract

Abnormalities in microvasculature and neovascular formation in the process of cardiac remodeling, and the relationship between angiogenesis and cardiac remodeling have not been elucidated, in dilated cardiomyopathy (DCM) and heart failure. To clarify the alterations in capillary microvasculature and the role of angiogenesis in cardiac remodeling, we examined the myocyte density, fibrous tissue volume, expression of genes relating to fibrosis, capillary density, and the expression of the genes for vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) at the ages of 5, 13, and 20 weeks and also investigated the effects of long-term treatment with amlodipine, nifedipine, and MCI-154 on capillary microvasculature and cardiac angiogenesis in hearts of the TO2 strain of cardiomyopathic hamster. Cardiomyopathic hamsters showed decreases in capillary density and proportion of venular capillaries concomitantly with a decrease in numerical myocyte density and enhanced expression of the genes for collagen I, collagen III, and transforming growth factor-β1, (TGF-β1,) leading to cardiac fibrosis. Long-term treatment with amlodipine and MCI-154 suppressed decreases in capillary density and the proportion of venular capillaries concomitantly with induction of VEGF and bFGE In conclusion, alterations in capillary microvasculature may be involved in the process of cardiac remodeling during dilated cardiomyopathy. Suppression of angiogenesis may be related to alterations in capillary microvasculature. Induction of cardiac angiogenesis may be a new strategy for the treatment of the remodeling process in dilated cardiomyopathy.