title: Fibroblast growth factor 2 is an essential cardioprotective factor in a closed-chest model of cardiac ischemia-reperfusion injury.
abstract: Fibroblast growth factor 2 (FGF2) is cardioprotective in in vivo models of myocardial infarction; however, whether FGF2 has a protective role in in vivo ischemia-reperfusion (IR) injury, a model that more closely mimics acute myocardial infarction in humans, is not known. To assess the cardioprotective efficacy of endogenous FGF2, mice lacking a functional Fgf2 gene (Fgf2(-/-)) and wild-type controls were subjected to closed-chest regional cardiac IR injury (90 min ischemia, 7 days reperfusion). Fgf2(-/-) mice had significantly increased myocardial infarct size and significantly worsened cardiac function compared to wild-type controls at both 1 and 7 days post-IR injury. Pathophysiological analysis showed that at 1 day after IR injury Fgf2(-/-) mice have worsened cardiac strain patterns and increased myocardial cell death. Furthermore, at 7 days post-IR injury, Fgf2(-/-) mice showed a significantly reduced cardiac hypertrophic response, decreased cardiac vessel density, and increased vessel diameter in the peri-infarct area compared to wild-type controls. These data reveal both acute cardioprotective and a longer term proangiogenic potential of endogenous FGF2 in a clinically relevant, in vivo, closed-chest regional cardiac IR injury model that mimics acute myocardial infarction.
authors: Division of Emergency Medicine, Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA Department of Developmental Biology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA.
authors: Stacey L
authors: SL
authors: House
authors: Division of Emergency Medicine, Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA Department of Developmental Biology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA.
authors: Joy
authors: J
authors: Wang
authors: Department of Developmental Biology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA.
authors: Angela M
authors: AM
authors: Castro
authors: Center for Cardiovascular Research, Department of Medicine, Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA.
authors: Carla
authors: C
authors: Weinheimer
authors: Center for Cardiovascular Research, Department of Medicine, Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA.
authors: Attila
authors: A
authors: Kovacs
authors: Department of Developmental Biology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA.
authors: David M
authors: DM
authors: Ornitz
keywords: Cardiac repair; FGF2; cardioprotection; fibroblast growth factor; ischemia‐reperfusion injury; myocardial infarction
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