TREATMENT WITH BONE MORPHOGENETIC PROTEIN 2 LIMITS INFARCT SIZE AFTER MYOCARDIAL INFARCTION IN MICE
TREATMENT WITH BONE MORPHOGENETIC PROTEIN 2 LIMITS INFARCT SIZE AFTER MYOCARDIAL INFARCTION IN MICE
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DOI：
10.1097/shk.0b013e318289728a
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发表时间：
2013-04-01
期刊：
影响因子：
3.1
通讯作者：
Braun, Thomas
中科院分区：
文献类型：
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作者：
Ebelt, Henning;Hillebrand, Ina;Braun, Thomas
已经设计了各种策略来减少心肌梗死的临床后果，包括急性医疗护理、血运重建、干细胞移植以及最近的预防心肌细胞死亡。胚胎信号通路的激活是一个特别有趣的选择，以补充这些策略，并提高心肌细胞的功能表现和存活率。在这里，我们集中在骨形态发生蛋白2（BMP-2），诱导异位形成的跳动的心肌细胞在中胚层的发展过程中，并保护新生心肌细胞缺血再灌注损伤。在急性心肌梗死的小鼠模型中，当在左前降支动脉结扎后静脉注射BMP-2时，小鼠的梗死面积减少。用BMP-2处理的小鼠的特征在于在梗塞的边缘区和远端心肌中的心肌细胞凋亡率降低。在体外，BMP-2增加了自发跳动的新生心肌细胞的频率和在2 Hz电起搏下的收缩性能，保留了细胞三磷酸腺苷储存，并降低了细胞凋亡率，尽管工作量增加。此外，BMP-2特异性诱导Smad 1/5/8蛋白的磷酸化，并保护成年心肌细胞免受长期缺氧诱导的细胞损伤和氧化应激，而不激活心肌细胞转化生长因子β途径。我们的数据表明，BMP-2治疗可能有相当大的治疗潜力，在个人与急性和慢性心肌缺血，改善心肌细胞的收缩力，防止心肌细胞死亡。
Various strategies have been devised to reduce the clinical consequences of myocardial infarction, including acute medical care, revascularization, stem cell transplantations, and more recently, prevention of cardiomyocyte cell death. Activation of embryonic signaling pathways is a particularly interesting option to complement these strategies and to improve the functional performance and survival rate of cardiomyocytes. Here, we have concentrated on bone morphogenetic protein 2 (BMP-2), which induces ectopic formation of beating cardiomyocytes during development in the mesoderm and protects neonatal cardiomyocytes from ischemia-reperfusion injury. In a mouse model of acute myocardial infarction, an i.v. injection of BMP-2 reduced infarct size in mice when given after left anterior descending artery ligation. Mice treated with BMP-2 are characterized by a reduced rate of apoptotic cardiomyocytes both in the border zone of the infarcts and in the remote myocardium. In vitro, BMP-2 increases the frequency of spontaneously beating neonatal cardiomyocytes and the contractile performance under electrical pacing at 2 Hz, preserves cellular adenosine triphosphate stores, and decreases the rate of apoptosis despite the increased workload. In addition, BMP-2 specifically induced phosphorylation of Smad1/5/8 proteins and protected adult cardiomyocytes from long-lasting hypoxia-induced cellular damage and oxidative stress without activation of the cardiodepressant transforming growth factor-beta pathway. Our data suggest that BMP-2 treatment may have considerable therapeutic potential in individuals with acute and chronic myocardial ischemia by improving the contractility of cardiomyocytes and preventing cardiomyocyte cell death.