Endothelial Factors and Myocardial Function

Abstract

The heart contains two types of endothelial cells, namely the vascular endothelial cells lining the coronary vessels and the endocardial endothelial cells lining the inner surfaces of the cardiac chambers. It is now recognised that these cardiac endothelial cells influence myocardial function through the paracrine release of a variety of diffusible substances (Shah 1996). The initial suggestion that endothelial cells influence myocardial function came from Brutsaert et al. (1988) who reported that selective denudation of the endocardial endothelium in isolated cardiac papillary muscle preparations altered contractile behaviour: the duration of twitch contraction was abbreviated and peak force slightly reduced. It was subsequently shown that endocardial endothelial cells modified the inotropic response of isolated papillary muscle preparations to various receptor-mediated agonists, analogous to endothelium-dependent regulation of vascular tone. In bioassay studies using cultured ventricular endocardial endothelial cells and isolated papillary muscle preparations, Shah and colleagues (Smith et al. 1991) demonstrated that these effects were mediated by the release of diffusible factors by endocardial cells. The physiological relevance of these in vitro findings has been controversial given that the endocardial endothelial monolayer in the whole heart is in close contact with only a tiny proportion of the total myocardial mass. In contrast, coronary microvascular endothelial cells are intimately apposed to cardiac myocytes throughout the heart, so that a physiologically relevant paracrine interaction is more plausible. Indeed, recent studies from a number of laboratories have confirmed the existence of such an interaction both in vitro and in humans in vivo.