The Role of Cell Proliferation and Apoptosis in the Cardiac Development

Kim, Eo Jin; Kim, Hyo Soo; Seo, Jeong Wook

Abstract

The functional and morphologic cardiac developments are determined by the morphogenesis, growth and remodeling of the heart resulted from the cell proliferation and apoptosis. We studied the distribution of the proliferation and apoptotic activity of myocardial cells according to the developmental stages in embryos of C57bl/6 mice. Serial histologic sections were stained with PCNA and TUNEL method and were analyzed with image analyzer (BMI, Seoul). The ventricular myocardium of an embryonic heart could be divided into trabecular, inner compact and outer compact layers. Proliferation indices at layers of the left ventricular myocardium on embryonal days (ED) 13, 14, 16, 17 and 18 were 19.9%/47.4%/60.4%, 16.1%/45.8%/60.3%, 24.6%/45.6%/38.1%, 23.3%/17.7%/18.3% and 31.2%/28.0%/19.4% (trabecular/ inner compact/ outer compact) and the right ventricle, 11.0%/34.4%/60.5%, 23.0%/44.0%/69.0%, 29.2%/42.9%/35.1%, 30.4%/30.5%/22.3% and 32.4%/28.4%/16.3%. The apoptotic indices of the left ventricle/VIF were 0.23%/3.66% on ED 13-14, 0.42%/1.31% on ED 16 and 0.05%/0.60% on ED 17-18. The results show that the proliferation of the myocytes was maximal at the outer compact layer on ED 13 and 14 but lowest on ED 17 and 18. This decrease was more pronounced at the left ventricle. The innermost trabecular layer showed a constant proliferation activity of 11.0-32.4%. The presence of spatiotemporal differences in the cell proliferation reveals regional regulation in the developmental timing of cardiac development. Functional maturation is considered to be responsible for the change of proliferation activity. The apoptosis was most frequent and intense in the VIF and crux throughout the periods of each embryonal day where as rarely seen in the ventricular myocardium, especially in the trabecular layer of myocardium. These findings suggest that the apoptosis plays the role in the development of atrioventricular, ventriculoarterial septation and valve formation. Our results also reveal that the participation of apoptosis in formation of the trabeculation can be denied.