Pathology, protein expression and signaling in myxomatous mitral valve degeneration: Comparison of dogs and humans

Myxomatous degenerative mitral valve disease (MMVD) is a common heart disease in dogs. Although several morphological similarities occur between human and canine MMVD differences exist. However, in advanced stages the accumulation of proteoglycans is the main finding in both species.The extracellular matrix (ECM) in normal canine and human mitral valves is similar. In MMVD of both species proteoglycans is the major alteration, although specific changes in collagen distribution exists.The valvular expression pattern of matrix metalloproteinases (MMPs) and of their inhibitors (TIMPs) differs, in part, between dogs and humans. The MMPs and TIMPs expression patterns are similar in normal canine and human mitral valves, but they are quite different during degenerative progression.Valve endothelial cells (VEC) and interstitial cells (VIC) are phenotypically transformed in canine and human MMVD. Inflammation is an unlikely cause of valve degeneration in humans and dogs. There are several lines of evidence suggesting that transforming growth factor β1 (TGF β1) and serotonin signaling may mediate valve degeneration in humans and dogs.Although human and canine MMVD share structural similarities, there are some differences in ECM changes, enzyme expression and cell transformation, which may reflect a varied pathogenesis of these diseases.