The influence of FGF2 high molecular weight (HMW) isoforms in the development of cardiac ischemia–reperfusion injury

Abstract Fibroblast growth factor 2 (FGF2) consists of multiple protein isoforms (low [LMW] and high molecular weight [HMW]), which are localized to different cellular compartments, indicating unique biological activity. We previously showed that the LMW isoform is important in protecting the heart from myocardial dysfunction associated with ischemia–reperfusion (I/R) injury, but the roles of the HMW isoforms remain unknown. To elucidate the role of HMW isoforms in I/R and cardioprotection, hearts from novel mouse models, in which the murine FGF2 HMWs are knocked out (HMWKO) or the human FGF2 24 kDa HMW isoform is overexpressed (HMW Tg) and their wildtype (Wt) or non-transgenic (NTg) cohorts were subjected to an ex vivo work-performing heart model of I/R. There was a significant improvement in post-ischemic recovery of cardiac function in HMWKO hearts (76 ± 5%, p p p