NEOVASCULARIZATION OF EMBRYONIC RAT HEARTS CULTURED IN OCULO CLOSELY MIMICS IN-UTERO CORONARY VESSEL DEVELOPMENT

Coronary neovascularization was studied following grafting of avascula r hearts from gestation day-12 (Er12) rat embryos to the anterior eye chambers of adult rats. Volume densities (V-v) of vessels, myocytes, a nd the extracellular matrix (ECM) after 3-7, 14, 21, and 35 days in oc ulo were compared to V-v in hearts developing in utero at E-15, E-18, and Er20. The myocardium in both models exhibited similar vessel V-v a nd capillary developmental stages: (1) clustering of endothelial cells and red blood cells; (2) endothelial cell migration, and (3) tube for mation/maturation. The V-v of myocytes increased while that of the ECM remained constant over time. Cross-species grafting utilizing species -specific antibodies determined that the majority, but not all, of the 10-day graft vasculature was of graft origin. Therefore, both de novo growth (vasculogenesis) and sprouting (angiogenesis) were occurring i n oculo. Tracer molecules infused into host rats reached the outermost graft vessels only after 10 days in oculo, suggesting a functional li nk with the host circulation after this time. Thus, we have shown that both models exhibit similar: (1) vascular V-v; (2) shifts in V-v of n onvascular components; (3) stages of neovascularization, and (4) mecha nisms of neovascularization. In conclusion, coronary neovascularizatio n occurring in oculo closely mimics normal coronary vessel development .