Molecular mechanisms of smooth muscle and fibroblast phenotype conversions in the failing heart

The mechanisms of gene regulation in cardiac hypertrophy and fibrosis are important in understanding the regulation of pathological gene expression in the heart. Cardiac hypertrophy is characterized by enlargement of the heart as a result of an increase in cardiomyocyte size and also enhanced fibrosis due primarily to phenotypic conversion of fibroblasts to myofibroblasts. Also, atherosclerosis, a disease characterized by formation of plaque within the arterial wall, and restenosis, which is the process of arterial wall healing in response to vascular injury, are highly affected by vascular remodelling. Vascular smooth muscle cells thus play a key role in vascular remodelling, as they modulate their phenotype in response to vascular injury and are a significant source of extracellular matrix components of the vessel wall. In view of the profound effects of both the fibroblast to myofibroblast conversion and also the role of vascular smooth muscle cells in vascular remodelling, we review the activation of the smooth muscle actin gene in these contexts to examine the common and non-overlapping molecular circuitry underlying these cellular processes in the cardiovascular system.