Fibroblast growth factor 2 is an essential cardioprotective factor in a closed-chest model of cardiac ischemia-reperfusion injury.
Fibroblast growth factor 2 is an essential cardioprotective factor in a closed-chest model of cardiac ischemia-reperfusion injury.
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DOI：
10.14814/phy2.12278
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发表时间：
2015-01-01
影响因子：
2.5
通讯作者：
Ornitz DM
中科院分区：
文献类型：
--
作者：
House SL;Wang J;Castro AM;Weinheimer C;Kovacs A;Ornitz DM
成纤维细胞生长因子2（FGF 2）在心肌梗死的体内模型中具有心脏保护作用;然而，FGF 2是否在体内缺血再灌注（IR）损伤中具有保护作用，这是一种更接近模拟人类急性心肌梗死的模型，尚不清楚。为了评估内源性FGF 2的心脏保护功效，使缺乏功能性Fgf 2基因（Fgf 2-/-）的小鼠和野生型对照经受闭胸局部心脏IR损伤（90分钟缺血，7天再灌注）。与野生型对照组相比，Fgf 2 −/−小鼠在IR损伤后1天和7天的心肌梗死面积显著增加，心脏功能显著恶化。病理生理学分析表明，在IR损伤后1天，Fgf 2 −/−小鼠的心脏应变模式恶化，心肌细胞死亡增加。此外，在IR损伤后7天，与野生型对照组相比，Fgf 2 −/−小鼠显示出显著降低的心脏肥大反应，降低的心脏血管密度和增加的梗死区血管直径。这些数据揭示了内源性FGF 2在模拟急性心肌梗死的临床相关体内闭胸局部心脏IR损伤模型中的急性心脏保护和长期促血管生成潜力。使用闭胸局部心脏IR损伤模型测试内源性FGF 2的心脏保护功效。在IR损伤后1天和7天，与野生型对照组相比，缺乏FGF 2的小鼠（Fgf 2 −/−）的心肌梗死面积显著增加，心脏功能显著恶化。这些数据揭示了内源性FGF 2在模拟急性心肌梗死的临床相关体内闭胸局部心脏IR损伤模型中的急性心脏保护和长期促血管生成潜力。
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. The cardioprotective efficacy of endogenous FGF2 was tested using a closed‐chest regional cardiac IR injury model. Mice lacking FGF2 (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. 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.