Abstract:

Canine myxomatous mitral valve disease （MMVD） is the most common heart disease and the most common cause of cardiac death in domestic dogs. Myxomatous degeneration of the mitral valve cannot be separated from the histological lesions of mitral valve cells. The most predominant lesion is deposition and degeneration of the extracellular matrix （ECM） of the valve. Activation of valve interstitial cells （VICs） into a myofibroblast phenotype is the source of the ECM lesion. There are multiple mechanisms for the activation of VICs. In the pathogenesis of MMVD， 5-hydroxytryptamine （5-HT） pathway is associated with changes in the physical and chemical environments of valves. The transforming growth factor-β （TGF-β） pathway is the main signalling pathway controlling the pathogenesis of MMVD and is associated with inflammation， mechanical forces and angiotensin in the animal organism. Bone morphogenetic proteins （BMPs） are associated with the developmental process of the animal organism. Reactive oxygen species （ROS） are involved in myocardial remodelling and heart failure and amplify the activation of MMVD by TGF-β， and a disintegrin and metalloproteinase thrombospondin motifs （ADAMTS） are associated with valve structure and function. At this stage， the treatment of MMVD antagonistic pathway drugs has emerged. 5-HT receptor antagonists attenuate VICs activation and MMVD-associated valve tissue lesions， and cytokines such as the cell membrane repair protein MG53 and fibroblast growth factor inhibit the TGF-β signalling pathway thereby treating MMVD. This article discusses three major aspects of MMVD histopathology， the mechanism of VICs activation， and the progress of research on therapeutic drugs for MMVD antagonistic pathways， in order to provide reference for in-depth research and clinical treatment of this disease.

Key words: canine; myxomatous mitral valve disease; valvular interstitial cells; signaling pathways