Understanding the molecular and cellular changes behind aortic valve stenosis.

Morbidity from degenerative aortic valve disease (AVS) is increasing worldwide, concomitant with the ageing of the population and the growing consumption of high caloric and cholesterol diets of the western countries. Despite the increasing prevalence of AVS, with its high mortality and morbidity, studies on the molecular and cellular mechanisms underlying the onset of aortic valve degeneration have only advanced in the last 15 years. The result of this effort is now beginning to reveal several mechanisms with great therapeutic targeting potential that may alter the natural history of this progressive pathology. Indeed, the view of this disease has changed from being an unmodifiable degenerative disease to an active biological process regulated by highly conserved cellular pathways. The progression of AVS includes inflammation, angiogenesis and remodelling of the extracellular matrix leading to osteogenesis in the aortic valve and revealing many mechanisms and risk factors similar to atherosclerosis. Therefore statins and angiotensin II antagonists seemed promising treatment options; however, experimental results are still controversial. Nonetheless, valvular degeneration results in dramatic myocardial changes induced by chronic pressure overload such as left ventricular hypertrophy as well as other paramount myocardial extracellular changes. Currently, a strong impulse for future research to investigate the pathophysiological mechanisms and their modulation in order to prevent/delay the onset or progression of valve degeneration is needed. In the present review, we focused on the molecular and cellular mechanisms underlying degenerative AVS and its myocardial impact.