Basic Fibroblast Growth Factor Attenuates Injury in Myocardial Infarction by Enhancing Hypoxia-Inducible Factor-1 Alpha Accumulation

• Main Authors: Zhiheng Rao, Danping Shen, Jiahui Chen, Lushen Jin, Xueping Wu, Ming Chen, Lei Li, Maoping Chu, Jiafeng Lin
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2020-08-01
• Series: Frontiers in Pharmacology
• Subjects: hypoxia-inducible factor-1 alpha; basic fibroblast growth factor (FGF2); ischemic cardiomyopathy; angiogenesis; antiapoptosis
• Online Access: https://www.frontiersin.org/article/10.3389/fphar.2020.01193/full

BackgroundThe combination of antiapoptotic and angiogenic actions may represent a pharmacotherapeutic strategy for the treatment of myocardial infarction. Fibroblast growth factor (FGF) is expressed in various cell types including endothelial and muscle cells and promotes their survival, migration, and proliferation.Methods and ResultsMyocardial microvascular endothelial cells were divided into four treatment groups, the sham, hypoxia, basic FGF (bFGF), and bFGF plus 2-methoxyestradiol groups, and subjected to in vitro apoptotic analysis and Matrigel assays. An in vivo model of myocardial infarction was established by ligaturing the left coronary artery of mice in the four treatment groups. Cardiac performance, myocardial injury, endothelial cell angiogenesis, and myocardial apoptosis were assessed. bFGF administration after myocardial infarction improved cardiac function and cell viability, attenuated myocardial injury and apoptosis, and enhanced angiogenesis. Western blotting of HIF-1α, p-AKT, VEGF, p53, BAX, and Bcl-2 showed that bFGF increased HIF-1α, p-AKT, VEGF, and Bcl-2 and decreased BAX protein levels.ConclusionThe results of the present study indicated that bFGF attenuates myocardial injury by inhibiting apoptosis and promoting angiogenesis via a novel HIF-1α-mediated mechanism and a potential utility of bFGF in protecting against myocardial infarction.