Cardiac Microvascular Endothelial Cells and Pressure Overload-Induced Cardiac Fibrosis

Abstract

Heart failure is one of the main causes of death worldwide. It is a consequence of ultimately maladaptive cardiac remodelling processes, i.e., hypertrophy, dilation, and fibrosis, that follow chronic pressure overload. Several cellular transformation processes induced by pressure overload result in the observed pathological changes in the heart: cardiomyocytes become hypertrophic, growing in both length and volume, thereby increasing myocardial wall thickness to reduce wall stress. Cardiac fibroblasts become activated to myofibroblasts, which produce large amounts of extracellular matrix resulting in a stiffening of the myocardium. Cardiac microvascular endothelial cells respond to the changed mechanical load either by transitioning towards an intermediate mesenchymal state producing extracellular matrix or by switching to a pro-fibrotic state reinforcing cardiac fibroblast to myofibroblast differentiation and thus excessive cardiac fibrosis and finally heart failure. Several factors have been shown to play a role in this endothelial cell dedifferentiation, such as transforming growth factor β1 and angiotensin II, and more are currently being assessed. This will pave the way for the development of long-sought therapeutic opportunities to prevent or stop excessive cardiac fibrosis and thus heart failure.