Etiology of valvular heart disease-genetic and developmental origins

Abstract

Valvular heart disease occurs as either a congenital or acquired condition and advances in medical care have resulted in valve disease becoming increasingly prevalent. Unfortunately, treatments remain inadequate because of our limited understanding of the genetic and molecular etiology of diseases affecting the heart valves. Therefore, surgical repair or replacement remains the most effective option, which comes with additional complications and no guarantee of life-long success. Over the past decade, there have been significant advances in our understanding of cardiac valve development and, not surprisingly, mutations in these developmental genes have been identified in humans with congenital valve malformations. Concurrently, there has been a greater realization that acquired valve disease is not simply a degenerative process. Molecular investigation of acquired valve disease has identified that numerous signaling pathways critical for normal valve development are re-expressed in diseased valves. This review will discuss recent advances in our understanding of the development of the heart valves, as well as the implications of these findings on the genetics of congenital and acquired valvular heart disease.

Figure 1.. Atrioventricular and semilunar valve structure.

Schematic demonstrating cellular architecture of atrioventricular and semilunar valves. Arrows, blood flow direction. Myo, myocardium; Ao, aortic. Reproduced with permission from Tao G, et al.

Figure 2.. Heart valve development and progression to calcific disease.

Valve development begins with endocardial cushion formation (A). Cushions grow to form valve primordial (B), which remodel into mature valve leaflet (C). Calcification of the valve leaflets occurs with disease (D) Reproduced with permission from Tao G, et al.