Increased endothelin-receptor density in myxomatous canine mitral valve leaflets

In dogs and humans, myxomatous mitral valve disease results in mitral valve prolapse and mitral regurgitation. Diseased leaflets display endothelial damage, which in turn might lead to subendothelial growth through release of paracrine mediators such as endothelin-1. The aim of the study was to investigate the presence and distribution of endothelin receptors and relate these to the presence and severity of myxomatous valve disease in the dog. Valves with clear macroscopic signs of disease were taken at postmortem from five old dogs. Control valves without macroscopic signs of disease were taken from five young dogs. Endothelin receptors in the leaflets were examined by using radiolabeled endothelin-1 detected by autoradiography. The endothelin-receptor density was graded semiquantitatively. To determine disease severity, adjacent sections stained with periodic acid-Schiff (PAS)/Alcian blue were examined histologically. The leaflet thickness was measured, and the mucopolysaccharide deposition, collagen degeneration, and fibrosis were graded semiquantitatively. Diseased areas displayed high endothelin-receptor densities; normal-looking areas showed low densities. The endothelin-receptor density within as well as on the leaflets correlated positively with all four measures of disease severity in the distal most affected third of the cusps, suggesting that endothelin plays a pathogenetic role in canine myxomatous mitral valve disease.