Cells and extracellular matrix interplay in cardiac valve disease: because age matters

Cardiovascular aging is a physiological process affecting all components of the heart. Despite the interest and experimental effort lavished on aging of cardiac cells, increasing evidence is pointing at the pivotal role of extracellular matrix (ECM) in cardiac aging. Structural and molecular changes in ECM composition during aging are at the root of significant functional modifications at the level of cardiac valve apparatus. Indeed, calcification or myxomatous degeneration of cardiac valves and their functional impairment can all be explained in light of age-related ECM alterations and the reciprocal interplay between altered ECM and cellular elements populating the leaflet, namely valvular interstitial cells and valvular endothelial cells, is additionally affecting valve function with striking reflexes on the clinical scenario. The initial experimental findings on this argument are underlining the need for a more comprehensive understanding on the biological mechanisms underlying ECM aging and remodeling as potentially constituting a pharmacological therapeutic target or a basis to improve existing prosthetic devices and treatment options. Given the lack of systematic knowledge on this topic, this review will focus on the ECM changes that occur during aging and on their clinical translational relevance and implications in the bedside scenario.