Tissue and cell renewal in the natural aortic valve of rats: an autoradiographic study

The present study has demonstrated that tissues of the aortic valve respond to the cyclic stresses of normal cardiac function by continual synthesis and renewal. Rats were injected with tritiated-precursors specific for proteins, ground substance components, and replicating DNA, and their sites of incorporation were identified autoradiographically. Extracellular component renewal and cell proliferation were greater in the fibrous connective tissue areas of the valve, namely the leaflet and attachment region, than in the musculoelastic sinus wall. Extracellular protein synthesis was greatest in the leaflet, whereas the highest glycosaminoglycan synthesis occurred in the attachment zone. Cellular replication, although infrequent, was equal in these fibrous regions, being higher than in the sinus wall. These observations may be explained by an analysis of the histology of the valve and consideration of the functional stresses to which the valve is subjected during the cardiac cycle. The leaflet is composed of layers of dense connective tissue oriented for maximum strength. On the other hand, the attachment zone represents a fibrous connective tissue designed for maximum flexibility; this area appears to function as a hinge. Cyclic operation of the valve causes damaging mechanical stresses in these regions, necessitating the continual regeneration of structural proteins required for strength and lubricative ground substance components required for flexibility. The sinus wall, composed of smooth muscle cells and elastic fibres, is undoubtedly better suited to cyclic tissue deformation, thereby explaining the lower synthetic levels of macromolecules. Due to the low level of cell replication, it seems reasonable to conclude that the functional stresses act to modulate the cell's secretory activity rather than to stimulate proliferation. Similar observations of stress-related tissue renewal have been reported.