Cardiovascular developmental insights from embryos

Abstract

We investigate cardiovascular (CV) developmental physiology and biomechanics in order to understand the dramatic acquisition of form and function during normal development and to identify the adaptive mechanisms that allow embryos to survive adverse genetic and epigenetic events. Cardiovascular patterning, morphogenesis, and growth occur via highly conserved genetic mechanisms. Structural and functional maturation of the embryonic heart is also conserved across a broad range of species with evidence for load dependence from onset of the heartbeat. The embryonic heart dynamically adapts to changes in biomechanical loading conditions and for reasons not yet clear, adapts better to increased than to decreased mechanical load. In mammals, maternal cardiovascular function dynamically impacts embryonic/fetal growth and hemodynamics and these interactions can now be studied longitudinally using high-resolution noninvasive techniques. Maternal exposure to hypoxia and to bioactive chemicals, such as caffeine, can rapidly impact embryonic/fetal cardiovascular function, growth, and outcome. Finally, tissue engineering approaches can be applied to investigate basic developmental aspects of the embryonic myocardium. We use isolated embryonic and fetal chick, mouse, or rat cardiac cells to generate 3D engineered early embryonic cardiac tissues (EEECT). EEECT retains the morphologic and proliferative features of embryonic myocardium, responds to increased mechanical load with myocyte hyperplasia, and may be an excellent future material for use in cardiac repair and regeneration. These insights into cardiovascular embryogenesis are relevant to identifying mechanisms for congenital cardiovascular malformations and for developing cell- and tissue-based strategies for myocardial repair.