Myocardial fibrosis in hypertensive heart disease: an overview of potential regulatory mechanisms

Myocardial fibrosis in hypertensive heart disease (HHD) can present as a reactive process, involving intramyocardial coronary arteries and arterioles with extensions of collagen into the neighbouring interstitial space, and as a replacement for necrotic cardiac myocytes. Fibrosis adversely affects myocardial stiffness and therefore regulatory mechanisms are of considerable interest. Mechanisms responsible for scarring (reparative fibrosis) are based on factors that adversely influence myocyte survival. This topic is not covered in this brief review. Mechanisms responsible for the perivascular/interstitial fibrosis that appear in both the normotensive, non-hypertrophied right and the pressure overloaded, hypertrophied left ventricule in HHD are addressed herein. They include: (a) angiotensin II (Ang II)-mediated coronary vascular hyperpermeability with subsequent fibrosis; (b) direct hormonal regulation of fibroblast collagen turnover, whereby Ang II, aldosterone and/or endothelins may be involved; (c) autocrine and paracrine signalling between fibroblasts and/or endothelial cells that alters collagen synthesis and degradation and which includes an angiotensin converting enzyme found in fibrous tissue. Collagen turnover in the myocardium is a dynamic process and fibrous tissue is anything but inert.