Cardiologie clinique et expérimentale
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Evidence of a Role for Tensile Loading in the Pathogenesis of Mitral Valve Degeneration

Carla M. R. Lacerda and E. Christopher Orton

Degenerative mitral valve disease (DMVD) is significant cause of cardiovascular morbidity and mortality in humans and dogs. Diseased valves present altered architecture, and distinct pathological characteristics including cell proliferation with phenotype transformation and extracellular matrix turnover with net deposition of proteoglycans, disorganization of collagen and fragmentation elastin. The specific triggers and mediators of leaflet degeneration and chordal rupture are largely unknown. Heart valves are very active tissues, capable of sustaining heavy cyclical loads. Indirect clinical evidence and direct experimental evidence support a hypothesis that DMVD might be initiated by abnormal tensile loading on valvular cells that in turn respond by inappropriate remodeling of the valve matrix. In this review, we present in vivo and in vitro studies linking leaflet or cellular strain to extracellular matrix turnover and expression of myxomatous markers similarly to DMVD. In addition, we discuss additional forces and stimuli that can act as mediators of myxomatous degeneration. Future studies elucidating mechanosensing signaling pathways involved in DMVD will be important to advancing understanding of its pathogenesis.