Recombinant human erythropoietin protects the myocardium from ischemia-reperfusion injury and promotes beneficial remodeling
Recombinant human erythropoietin protects the myocardium from ischemia-reperfusion injury and promotes beneficial remodeling
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DOI：
10.1073/pnas.0630444100
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发表时间：
2003-04-15
影响因子：
11.1
通讯作者：
Brines, M
中科院分区：
文献类型：
--
作者：
Calvillo, L;Latini, R;Brines, M
促红细胞生成素（EPO）是细胞因子超家族的成员之一，它在促进红细胞存活和分化中起重要作用。最近的研究已经确定了EPO的多种旁分泌/自分泌功能，其通过维持来协调对损伤的局部反应。血管自动调节和减弱细胞死亡的主要（凋亡）和次要（炎性）原因。实验证据也支持EPO在脑和脊髓损伤后的修复和再生中的作用，包括将干细胞募集到损伤区域。EPO受体的组织表达是广泛的，特别是在发育期间，并且包括心脏。然而，目前尚不清楚EPO是否在成人心肌组织中发挥生理功能。我们已经评估了EPO在体外对成年大鼠心肌细胞的潜在保护作用，以及在大鼠心肌梗死再灌注模型中的体内保护作用。结果表明，EPO对缺氧28 h（约3%常氧）培养的成年大鼠心肌细胞凋亡有明显的抑制作用。采用大鼠冠状动脉缺血-再灌注模型的其他研究表明，施用重组人EPO（5，000单位/kg体重;每天腹膜内注射，持续7天）使心肌细胞损失减少约50%，这一程度足以在再灌注后1周内使血液动力学功能正常化。这些观察结果不仅表明重组人EPO通过防止细胞凋亡和减轻梗死后血流动力学功能的恶化在治疗心肌缺血和梗死中具有潜在的治疗作用，而且还预测EPO可能是其他器官中的组织保护性细胞因子。
Erythropoietin (EPO), originally identified for its critical hormonal role in promoting erythrocyte survival and differentiation, is a member of the large and diverse cytokine superfamily. Recent studies have identified multiple paracrine/autocrine functions of EPO that coordinate local responses to injury by maintaining. vascular autoregulation and attenuating both primary (apoptotic) and secondary (inflammatory) causes of cell death. Experimental evidence also supports a role for EPO in repair and regeneration after brain and spinal cord injury, including the recruitment of stem cells into the region of damage. Tissue expression of the EPO receptor is widespread, especially during development, and includes the heart. However, it is currently unknown as to whether EPO plays a physiological function in adult myocardial tissue. We have assessed the potential protective role of EPO in vitro with adult rat cardiomyocytes, and in vivo in a rat model of myocardial infarction with reperfusion. The results show that EPO markedly prevents the apoptosis of cultured adult rat myocardiocytes subjected to 28 h of hypoxia (approximate to3% normal oxygen). Additional studies employing a rat model of coronary ischemia-reperfusion showed that the administration of recombinant human EPO (5,000 units/kg of body weight; i.p. daily for 7 days) reduces cardiomyocyte loss by approximate to50%, an extent sufficient to normalize hemodynamic function within 1 week after reperfusion. These observations not only suggest a potential therapeutic role for recombinant human EPO in the treatment of myocardial ischemia and infarction by preventing apoptosis and attenuating postinfarct deterioration in hemodynamic function, but also predict that EPO is likely a tissue-protective cytokine in other organs as well.