Also supporting this hypothesis, in vitro experiments of Lacerda and colleagues showed that canine mitral leaflets undergoing static and cyclic strains, compared to unstrained controls, express increased amount of activated interstitial cell phenotype markers, glycosaminoglycans synthetic enzymes, proteoglycans, extracellular matrix catabolic enzymes, and TPH1 [14]; however, a pig model of MR failed to show increased mitral valve (MV) expression of TPH1 compared to controls [9]. This evidence concerns the gene TPH1 and miotic rate.