The interaction of coronary tone and cardiac fibrosis.

Regulation of coronary vascular tone is critical for proper perfusion and function of the myocardium. Many disease processes result in compromised regulation of coronary vascular tone and impaired myocardial perfusion. A common result of coronary vascular dysfunction is the development of areas of replacement fibrosis within the myocardium and surrounding the vasculature. Both intravascular processes, such as coronary atherosclerosis and endothelial dysfunction, and extravascular processes, including compromised myocardial metabolism, hormone excesses, and altered local signaling, may result in coronary vascular dysregulation. Coronary occlusion events, in turn, lead to myocardial damage and the activation of inflammatory cells and fibroblasts. The role of fibroblasts in regulating myocardial fibrosis and the contribution of myofibroblasts, cells that have limited contractile potential while retaining many of the extracellular matrix regulating processes of the fibroblast, may also contribute to the development of myocardial disease. In this review we examine the recent literature on myocardial fibrosis and myofibroblast activity, highlighting the effects of several classes of cardiovascular agents on the remodeling process.