Basic fibroblast growth factor is cardioprotective in ischemia-reperfusion injury

Abstract

To examine whether basic fibroblast growth factor (bFGF) administered to the heart by perfusion can improve cardiac resistance to injury we employed an isolated rat heart model of ischemia-reperfusion injury and determined the extent of functional recovery in bFGF-treated and control hearts. Global ischemia was simulated by interruption of flow for 60 min. Recovery of developed force of contraction (DF), recorded after reestablishment of flow for 30 min, reached 63.8 +/- 1.5% and 96.5 +/- 3.5% of preischemic levels in control and bFGF-treated hearts (10 micrograms/heart), respectively, indicating that bFGF induced significantly improved recovery of mechanical function. Recoveries of the rates of contraction or relaxation were also significantly improved in bFGF-treated hearts. Extent of myocardial injury, assessed by determination of phosphocreatine kinase in the effluent, was reduced as a result of bFGF treatment. As a first step towards understanding the mechanism and direct cellular target(s) of bFGF-induced cardioprotection, we investigated its fate after perfusion. Perfusion of 10 micrograms bFGF/heart resulted in a 4-fold increase in bFGF associated with the heart compared to control levels, as estimated by biochemical fractionation and immunoblotting. Immunofluorescent staining of the bFGF-perfused hearts revealed intense anti-bFGF staining in association with blood vessels as well as the periphery of cardiomyocytes, suggesting that the latter may be a target for direct bFGF action. In conclusion, our findings of bFGF-induced increases in cardiac resistance to, and improved functional recovery from, ischemia-reperfusion injury indicate that bFGF may have clinical applications in the treatment of ischemic heart disease.

The cardioprotective effect of the low molecular weight isoform of fibroblast growth factor-2: The role of JNK signaling

“…Interestingly, FGF2 LMWKO mouse hearts, in which only the FGF2 HMW isoforms are present, had a percent recovery of post-ischemic contractile function similar to mice deficient in all LMW and HMW isoforms ( Figure 5). This observation suggests that the LMW isoform is responsible for protecting the heart from myocardial dysfunction which is consistent with that reported by the Kardami group [9,14]. A question remains as to what roles, if any, do the HMW isoforms of FGF2 have in cardioprotection and ischemia-reperfusion injury.…”

“…Although FGF2 LMW and HMW isoforms have different biological functions in several in vitro studies, the question remains as to the role of specific FGF2 isoform(s) in I/R injury and cardioprotection. Kardami and colleagues demonstrated that treatment with the FGF2 LMW isoform improved cell survival and functional recovery in the ischemic rat heart [14] and also that overexpression of the FGF2 LMW isoform in mice reduced cardiomyocyte damage [9]. In the present study, the role of FGF2 LMW isoform in I/R injury was elucidated by subjecting novel mouse models to I/R injury.…”

“…Many studies have demonstrated that FGF2 is a cardioprotective molecule [2,12,14]. Our laboratory previously showed that FGF2 is very important in protecting the heart from myocardial dysfunction and myocardial infarction following ischemia-reperfusion (I/R) injury [12].…”

“…Our laboratory has recently reported that overexpressing FGF2 in the heart can protect against contractile dysfunction and myocardial infarction caused by ischemiareperfusion (I/R) injury, and this cardioprotective effect is independent from its angiogenic activity [12]. Although FGF2 is a known cardioprotective molecule [2,[12][13][14], the function(s) of the LMW and HMW protein isoforms in I/R injury and cardioprotection remain to be elucidated.…”

Elevated Circulating Levels of Basic Fibroblast Growth Factor and Vascular Endothelial Growth Factor in Patients With Acute Myocardial Infarction

“…In addition, Padua et al reported that, in the rat, damage from an injury to the myocardial tissues of a bFGF-treated heart was less than in a control heart, and they suggested that bFGF has a direct cardioprotective effect. 40 Taking all the results together, bFGF may be correlated with the wound healing processes in injured myocardial tissue.…”