Acidic and basic fibroblast growth factors involved in cardiac angiogenesis following infarction.

Acidic and basic fibroblast growth factors (FGF-1/FGF-2) promote angiogenesis in cancer. Angiogenesis is integral to cardiac repair following myocardial infarction (MI). The potential regulation of FGF-1/FGF-2 in cardiac angiogenesis postMI remains unexplored. Herein, we examined the temporal and spatial expression of FGF-1/FGF-2 and FGF receptors (FGFR) in the infarcted rat heart at days 1, 3, 7, and 14 postMI. FGF-1/-2 gene and protein expression, cells expressing FGF-1/-2 and FGFR expression were examined by quantitative in situ hybridization, RT-PCR; western blot, immunohistochemistry and quantitative in vitro autoradiography. Compared to the normal heart, we found that in the border zone and infarcted myocardium 1) FGF-1 gene expression was increased in the first week postMI and returned to control levels at week 2; FGF-1 protein levels were, however, largely reduced at day 1, then elevated at day 3 peaked at day 7 and declined at day 14; and cells expressing FGF-1 were primarily inflammatory cells; 2) FGF-2 gene expression was significantly elevated from day 1 to day 14; the increase in FGF-2 protein level was most evident at day 7 and cells expressing FGF-2 were primarily endothelial cells; 3) FGFR expression started to increase at day 3 and remained elevated thereafter; and 4) FGF-1/FGF-2 and FGFR expression remained unchanged in the noninfarcted myocardium. Thus, FGF-1/FGF-2 and FGFR expression are enhanced in the infarcted myocardium in the early stage after MI, which is spatially and temporally coincident with angiogenesis, suggesting that FGF-1/FGF-2 are involved in regulating cardiac angiogenesis and repair.