Role of Angiogenetic Factors in Cardiac Valve Homeostasis and Disease

The aging of populations worldwide and the habitual consumption of food high in calories and cholesterol have led to recent increases in morbidity from calcific aortic valve disease. At the same time, rupture of the chordae tendineae cordis, which is a component of the mitral valve complex, is one of the major causes of mitral regurgitation. Surgery is the basis of treatment for these diseases, and little is known about their causes and mechanisms. A balance of angiogenetic and angioinhibitory factors is crucial for normal development and homeostasis of many organs. Although the heart is a vascular-rich organ, most of the cardiac valve complex is avascular like cartilage and tendons. Our studies have focused on the role of angiogenetic factors expressed in the cartilage and tendons in cardiac valve homeostasis. Recently, we found that chondromodulin-I, tenomodulin, and periostin play essential roles in degeneration and/or rupture of the cardiac valve complex by controlling angiogenesis and matrix metalloproteinase production. Here, we review the mechanistic insights provided by these studies and the proposed roles of angiogenetic factors in cardiac valve homeostasis and disease.