EARLY CORONARY ANGIOGENESIS IN RESPONSE TO THYROXINE - GROWTH-CHARACTERISTICS AND UP-REGULATION OF BASIC FIBROBLAST GROWTH-FACTOR

Although a substantial coronary angiogenesis occurs after thyroid horm one treatment,its regulation and relationship to cardiac hypertrophy a re not understood. This study aias designed to determine (1) the onset of capillary proliferation, (2) the sites of capillary proliferation, and (3) whether basic fibroblast growth factor (bFGF) upregulation oc curs in response to thyroxine administration. Male Sprague-Dawley rats were injected daily With L-thyroxine (T-4, 0.2 mg/kg SC). Bromodeoxyu ridine labeling of capillary endothelial cells increased during the fi rst 2 1 hours of treatment and peaked after 2 days of treatment. North ern blot analysis revealed a slight increase in bFGF mRNA during this period, followed by a doubling of expression by 48 hours, at which tim e bFGF protein was also increased. In situ hybridization, used to loca lize bFGF mRNA, showed an increase in transcripts within 24 hours afte r T-4. This enhancement was uniform in the epimyocardium and endomyoca rdium. Histochemical analysis (double staining for alkaline phosphatas e and dipeptidyl peptidase) of frozen sections, used to discriminate c apillary profiles as arteriolar and venular, respectively, showed that growth occurred in the latter, since the percentage of capillary prof iles positive for dipeptidyl peptidase was higher than the control val ue after 4 days of T-4 administration. These data indicate that in the thyroxine model of cardiac hypertrophy (1) capillary DNA synthesis oc curs after a single injection of thyroxine, (2) capillary growth coinc ides with an upregulation in bFGF mRNA and increase in bFGF protein, a nd (3) proliferation occurs in the venular capillaries.