Induction of cardiomyocyte calcification is dependent on FoxO1/NFATc3/Runx2 signaling

Cardiovascular disorders (CAVDs) being a major concern over the past several years due to the huge number of morbidity and mortality worldwide, a number of studies have been done on the various aspects of cardiac problems. One of the various CAVDs is cardiovascular calcification. A number of investigations and research work have been done previously on the molecular mechanism of vascular and heart valve calcification but the mechanism of myocardial and cardiomyocyte calcification has remained uninvestigated. A number of case studies have shown the presence of calcific deposits in the myocardial/ventricular region of the heart in fetal condition as well as in individuals of different ages but no detailed studies have been done yet. In this study, we have mainly investigated the role of Forkhead box transcription factor FoxO1 and nuclear factor of activated T-cells NFATc3 in cardiomyocyte calcification. Our studies in H9c2 cardiomyocytes show that calcific deposition in cardiomyocytes does not occur in 15 d but upon osteogenic induction for 1 mo where FoxO1 expression gets reduced thereby increasing the expression of its downstream target NFATc3, thus increasing the expression of the osteogenic marker Runx2. Detailed studies on the molecular mechanism of cardiomyocyte calcification will help in finding out therapeutic strategies in the treatment of cardiac calcification.