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

Abstract

Background: The 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 Results: Myocardial microvascular endothelial cells were divided into four treatment groups, the sham, hypoxia, basic FGF (bFGF), and bFGF plus 2methoxyestradiol 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-1a, p-AKT, VEGF, p53, BAX, and Bcl-2 showed that bFGF increased HIF-1a, p-AKT, VEGF, and Bcl-2 and decreased BAX protein levels. Conclusion: The results of the present study indicated that bFGF attenuates myocardial injury by inhibiting apoptosis and promoting angiogenesis via a novel HIF-1a-mediated mechanism and a potential utility of bFGF in protecting against myocardial infarction.

Macro‐encapsulation of mesenchymal stem cells in acute and chronic liver injury animal models

“…It is not clear from our results alone how encapsulated MSCs promote the secretion of growth hormones. However, several studies have suggested that HIF‐1α promotes the secretion of growth hormones such as VEGF and FGF 30,31 . We also confirmed that hypoxic conditions occurred in the encapsulated MSCs (Fig.…”

“…However, several studies have suggested that HIF-1α promotes the secretion of growth hormones such as VEGF and FGF. 30,31 We also confirmed that hypoxic conditions occurred in the encapsulated MSCs (Fig. 6c) and that growth hormone levels were higher in encapsulated MSCs than in monolayer culture conditions.…”

The Multifunctional Contribution of FGF Signaling to Cardiac Development, Homeostasis, Disease and Repair

“…Positive modulatory effects of FGF1 and FGF2 in the repair of induced ischemia-reperfusion injury and MI were revealed to be based on cardiomyocyte proliferation, stimulation of angiogenesis and the recovery of MI-induced remodeling, systolic and diastolic activities of the heart ( Engel et al, 2006 ; Formiga et al, 2014 ; Garbayo et al, 2016 ; Rao et al, 2020 ). This repairing function of FGF1 is further improved by co-treatment of FGF1 with an inhibitor of p38 MAPK.…”

“…The action of Fgfr2 overexpression together with the reduction in cardiomyocyte apoptosis after MI is correlated to upregulation of Fgf2 and its autocrine effect ( Matsunaga et al, 2009 ). Anti-apoptotic and pro-angiogenic protective responses following FGF2 treatment after MI in mice were induced through activation of the AKT-hypoxia-inducible factor-1 alpha (HIF-1α)-VEGF axis ( Rao et al, 2020 ). In cardiac regeneration of the zebrafish after injury, the active presence of the FGF-AKT signaling cascade is required for the survival of cardiomyocytes ( Tahara et al, 2021 ).…”

Role of miRNA-324-5p-Modified Adipose-Derived Stem Cells in Post-Myocardial Infarction Repair

“…Heart was exposed in the fourth and fifth intercostal gap after left thoracotomy, when left anterior descending coronary artery (LAD) running in myocardial tissues consistent with the direction of the great myocardial vein was found, it was sutured and ligated with 6-0 silk thread. After LAD occlusion, the corresponding blood supply area was whitened, while infarction manifestations such as ST segment elevation was noticed as electrocardiogram displayed ( 11 , 18 , 20 - 23 ). Subsequent treatments were performed 30 min after ligation ( 22 ).…”