CORONARY VASCULARIZATION DURING DEVELOPMENT IN THE RAT AND ITS RELATIONSHIP TO BASIC FIBROBLAST GROWTH-FACTOR

Objective: Our overall aims were to elucidate the temporal and spatial sequence of coronary vascularization during development in the rat, a nd to determine whether basic fibroblast growth factor expression corr esponds to any phase of the vascularization process. Methods: Immunohi stochemical, histochemical, morphometric and in situ hybridization ana lyses were performed on prenatal and postnatal hearts of various ages. Results: Coronary vascularization, which begins at embryonic day 13 ( E13) with blood island-like structures in the epicardium, progresses f rom this layer toward the endocardium as indicated by a transmural gra dient of vascular volume throughout the ventricles. Vascular smooth mu scle first appears in E17 hearts at the time a capillary-like plexus c oalesces and penetrates the aorta to form the main coronary arteries. These vessels maintain an anastomatic morphology and must undergo subs equent remodeling in order to assume adult branching characteristics. The early postnatal period is characterized by development of the arte rial tree and the enzymatic differentiation of the arteriolar and venu lar ends of the capillary bed. Although bFGF is expressed both prenata lly and postnatally, the highest mRNA expression was noted during the early period of vascularization (E14 and E15), and the early neonatal period (1-6 days) which corresponds to a period of substantial microva scular growth. Conclusions: Coronary vascularization follows a tempora l sequence which includes transmural expansion of the capillary bed, a rteriolar formation subsequent to vascular penetration of the aorta, a nd postnatal growth, differentiation, and remodeling. Since high level s of bFGF expression are correlated with key time points in coronary v ascular growth, bFGF may play an important role in this process.