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 d amage, which in turn might lead to subendothelial growth through release of paracrine mediators such as endothelin-1. The aim of the study was to inve stigate the presence and distribution of endothelin receptors and relate th ese to the presence and severity of myxomatous valve disease in the dog. Va lves with clear macroscopic signs of disease were taken at postmortem from five old dogs. Control valves without macroscopic signs of disease were tak en from five young dogs. Endothelin receptors in the leaflets were examined by using radiolabeled endothelin-1 detected by autoradiography. The endoth elin-receptor density was graded semiquantitatively. To determine disease s everity, adjacent sections stained with periodic acid-Schiff (PAS)/Alcian b lue were examined histologically. The leaflet thickness was measured, and t he mucopolysaccharide deposition, collagen degeneration, and fibrosis were graded semiquantitatively. Diseased areas displayed high endothelin-recepto r densities; normal-looking areas showed low densities. The endothelin-rece ptor density within as well as on the leaflets correlated positively with a ll four measures of disease severity in the distal most affected third of t he cusps, suggesting that endothelin plays a pathogenetic role in canine my xomatous mitral valve disease.