Morphoregulatory interactions of endocardial endothelium and extracellular material in the heart

The endocardium forms the inner lining of the cavities of the heart. The luminal surface of the cardiac wall is subjected to considerable cyclical physico-chemical forces. These forces can have structural and physiological consequences both for the endocardial endothelium and for the subjacent interstitial tissue. In the latter tissue space, the extracellular matrix (ECM) plays a dominant role during cardiogenesis. For example, this role becomes evident from the influence of fibronectin in the directional migration of proendocardial cells and in the formation of a trabeculated heart. In particular, the complex processes occurring in the valves of the developing heart illustrate a spatiotemporally regulated expression of ECM components and adhesion molecules. In the adult heart, the endocardial interstitial tissue consists of a thin basal lamina, a reticular lamina and a fibroelastic layer which contains some fibroblasts, smooth muscle cells and a heterogeneous population of nerve fibers. Unlike in arteries, elastic fiber in the fibroelastic layer of ventricular endocardium do not constitute an elastic lamina. Differences in thickness of the endocardium between atria and ventricles, as well as the diffuse and focal endocardial fibrosis during ageing have been related to mechanical stress and local turbulence of flow. Although endocardial fibrosis is a common pathological finding in various cardiomyopathies, our knowledge on the structural organization and on the pathogenetic role of ECM is very limited, mainly by the lack of suitable experimental models.