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

Journal of Molecular and Cellular Cardiology
Siyun LiaoJo El J Schultz

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<0.05) compared to Wt hearts (55+/-5%), with a corresponding decrease in HMW Tg function (line 20: 38+/-6% and line 28: 33+/-4%, p<0.05) compared to non-transgenic hearts (68+/-9%). FGF2 LMW isoform was secreted from Wt and HMWKO hearts during I/R, and a FGF receptor (FGFR) inhibitor, PD173074 caused a decrease in cardiac function when administered in I/R in Wt and FGF2 HMWKO he...Continue Reading

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Citations

Nov 19, 2013·Physiological Reports·Eyad NusayrTom Doetschman
Nov 19, 2013·Physiological Reports·Eyad Nusayr, Tom Doetschman
Mar 13, 2013·American Journal of Physiology. Heart and Circulatory Physiology·Janet R ManningJo El J Schultz
Apr 24, 2020·Frontiers in Pharmacology·Lian-Cheng DengJin-San Zhang
Nov 13, 2014·The Journal of Biological Chemistry·Collin Homer-BouthietteMarja M Hurley
May 31, 2016·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·Jayanta GuptaDavid J Margolis
Mar 20, 2019·The International Journal of Neuroscience·Hong KeGuangkun Feng
Jan 6, 2021·International Journal of Molecular Sciences·Friederike Freiin von HövelClaudia Grothe
Dec 16, 2020·International Journal of Molecular Sciences·Márton Richárd SzabóCsaba Csonka
Jun 8, 2021·Frontiers in Cell and Developmental Biology·Farhad KhosraviHeinrich Sauer

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