Cardiovascular Patterning as Determined by Hemodynamic Forces and Blood Vessel Genetics

BACKGROUND: Vascular patterning depends on coordinated timing of arteriovenous specification of endothelial cells and the concomitant hemodynamic forces supplied by the onset of cardiac function. Using a combination of 3D imaging by OPT and embryo registration techniques, we sought to identify structural differences between three different mouse models of cardiovascular perturbation. RESULTS: Endoglin mutant mice shared a high degree of similarity to Mlc2a mutant mice, which have been shown to have a primary developmental heart defect causing secondary vessel remodeling failures. Dll4 mutant mice, which have well-characterized arterial blood vessel specification defects, showed distinct differences in vascular patterning when compared to the disruptions seen in Mlc2a (-/-) and Eng (-/-) models. While Mlc2a (-/-) and Eng (-/-) embryos exhibited significantly larger atria than wild-type, Dll4 (-/-) embryos had significantly smaller hearts than wild-type, but this quantitative volume decrease was not limited to the developing atrium. Dll4 (-/-) embryos also had atretic dorsal aortae and smaller trunks, suggesting that the cardiac abnormalities were secondary to primary arterial blood vessel specification defects. CONCLUSIONS: The similarities in Eng (-/-) and Mlc2a (-/-) embryos suggest that Eng (-/-) mice may suffer from a primary heart developmental defect and secondary defects in vessel patterning, while defects in Dll4 (-/-) embryos are consistent with primary defects in vessel patterning.