Coronary anomalies in mice with congenital heart defects

Background: Coronary anomalies are frequently associated with congenital cardiac defects. Accordingly, we tested the hypothesis that the development of the tunica media of coronary arteries/arterioles is compromised in mice with cardiac defects of the outflow tract (persistent truncus arteriosus, double outlet right ventricle and transposition of the great arteries) by studying hearts of G7-9 generation mice bred from mutagenized mice caused by N-ethyl-N-nitrosourea. Mice were studied at embryonic days E16.5, E17.5, and postnatal days 1 and 11. Data were based on immunohistochemistry of serial sections.

Results: In 21 of 24 mice with outflow tract defects, the development of smooth muscle in arteries and arterioles was retarded; most commonly arterioles had an incomplete layer of smooth muscle or in a few instances, lacked a tunica media. In this model, an absence of a coronary ostium occurred in only 2 mice, indicating that the mechanisms underlying the formation of coronary ostia and the recruitment and differentiation of vascular smooth muscle differ. Coronary fistulas were present in 20% and dilated vessels in 30% of the hearts with cardiac defects.

Conclusions: The data suggest that vascular smooth muscle recruitment and differentiation are not necessarily linked to other coronary anomalies, such as absence of a main coronary artery or branching patterns.