[Aortic stenosis and extracellular matrix remodeling]

Abstract

Valvular heart diseases represent an important public health burden. With the decrease in the incidence of rheumatic heart disease, calcific aortic stenosis has now become the most common valvular disease in Western countries. Its prevalence increases with age, such that its affects about 4% of the elderly population and it is the most common motive for valve replacement. Several tissue abnormalities were observed in aortic valves from patients suffering from aortic stenosis: presence of large calcium deposits, inflammatory cells, lipids, and neocapillaries as well as extracellular matrix remodeling. The aortic valves show three characteristic layers: the fibrosa composed mainly of collagen bundles, the spongiosa which consists of a proteoglycan matrix, and the ventricularis which contains several elastic lamellae. The components of the extracellular matrix are synthesized by valvular mesenchymal cells. The turn-over of collagen and elastic fibers is low; the other macromolecules are more rapidly synthesized and hydrolysed. Serine proteases such as enzymes of the fibrinolytic system and matrix metalloproteinases play a role in the remodeling of the extracellular matrix. The hydrolysis of adhesive proteins, such as fibronectin, by plasmin triggers the apoptosis of valvular (myo)fibroblasts, a biological process named anoikis. Cellular events and extracellular matrix remodeling thus participate to the evolution of aortic valves towards aortic stenosis.