Coronary anomalies in mice with congenital heart defects
Robert J Tomanek1, Qing Yu, Cecilia W Lo
1Department of Anatomy and Cell Biology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa.
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.
Insights
Congenital heart defects in mice can impair coronary artery smooth muscle development. This study found that smooth muscle defects in coronary arteries and arterioles are common in outflow tract cardiac defects.
Area of Science:
- Cardiovascular Research
- Developmental Biology
- Medical Genetics
Background:
- Coronary anomalies often accompany congenital cardiac defects.
- Investigated the tunica media development in coronary arteries/arterioles of mice with outflow tract defects.
- Utilized mutagenized mice (N-ethyl-N-nitrosourea) for G7-9 generation studies.
Purpose of the Study:
- To test if tunica media development is compromised in mice with outflow tract cardiac defects.
- To understand the relationship between smooth muscle development and other coronary anomalies.
Main Methods:
- Studied mouse hearts at embryonic days E16.5, E17.5, and postnatal days 1 and 11.
- Employed immunohistochemistry on serial sections for data collection.
Main Results:
- Retarded smooth muscle development observed in 21 of 24 mice with outflow tract defects.
- Arterioles frequently showed incomplete or absent tunica media.
- Coronary fistulas (20%) and dilated vessels (30%) were noted in affected hearts.
Conclusions:
- Vascular smooth muscle recruitment and differentiation are not always linked to other coronary anomalies.
- Mechanisms for coronary ostia formation and vascular smooth muscle development appear distinct.
