Myocardial infarction induces embryonic reprogramming of epicardial c-kit+ cells: Role of the pericardial fluid
Myocardial infarction induces embryonic reprogramming of epicardial c-kit+ cells: Role of the pericardial fluid
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DOI：
10.1016/j.yjmcc.2009.11.008
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发表时间：
2010-04-01
影响因子：
5
通讯作者：
Capogrossi, Maurizio C.
中科院分区：
文献类型：
--
作者：
Limana, Federica;Bertolami, Chiara;Capogrossi, Maurizio C.
在成人心外膜中发现了表达c-kit的干细胞。在小鼠中，心肌梗死后，这些细胞增殖，迁移到损伤部位并向心肌和血管表型分化。我们假设，急性心肌梗死后，心包囊的完整性和心包液（PF）可能发挥作用的心外膜细胞的基因表达，增殖和分化。微阵列分析表明，在存在一个完整的心包，心肌梗死调制246个基因在心外膜细胞，其中大部分是与细胞增殖，细胞骨架组织，伤口修复和信号转导。有趣的是，WT 1，Tbx 18和RALDH 2，特别是参与心外膜胚胎发育，显着上调。重要的是，共表达的干细胞抗原c-kit和WT 1和/或Tbx 18的免疫组化检测在小鼠心外膜在胚胎发育过程中，以及在成年小鼠梗死的心脏。将急性心肌缺血（PFMI）患者的人心包液注射到非梗死小鼠心脏的心包腔内，增强了心外膜细胞增殖和WT 1表达。此外，PFMI补充缺氧培养的人心外膜c-kit（+）细胞增加WT 1和Tbx 18 mRNA的表达。最后，胰岛素样生长因子1，肝细胞生长因子和高迁移率族蛋白1，以前参与心脏c-kit（+）细胞的增殖和分化，在PFMI增加相比，非缺血性患者的心包液。总之，心肌梗死重新激活了心外膜c-kit（+）细胞的胚胎程序;心肌坏死后心包液中释放的可溶性因子可能在此过程中发挥作用。(c)2009爱思唯尔有限公司保留所有权利。
Stem cells expressing c-kit have been identified in the adult epicardium. In mice, after myocardial infarction, these cells proliferate, migrate to the injury site and differentiate toward myocardial and vascular phenotype. We hypothesized that, acutely after myocardial infarction, pericardial sac integrity and pericardial fluid (PF) may play a role on epicardial cell gene expression, proliferation and differentiation. Microarray analysis indicated that, in the presence of an intact pericardial sac, myocardial infarction modulated 246 genes in epicardial cells most of which were related to cell proliferation, cytoskeletal organization, wound repair and signal transduction. Interestingly, WT1, Tbx18 and RALDH2, notably involved in epicardial embryonic development, were markedly up-regulated. Importantly, coexpression of stem cell antigen c-kit and WT1 and/or Tbx18 was detected by immunohistochemistry in the mouse epicardium during embryogenesis as well as in adult mouse infarcted heart. Injection of human pericardial fluid from patients with acute myocardial ischemia (PFMI) in the pericardial cavity of non-infarcted mouse hearts, enhanced, epicardial cell proliferation and WT1 expression. Further, PFMI supplementation to hypoxic cultured human epicardial c-kit(+) cells increased WT1 and Tbx18 mRNA expression. Finally, insulin-like growth factor 1, hepatocyte growth factor and high mobility group box 1 protein, previously involved in cardiac c-kit(+) cell proliferation and differentiation, were increased in PFMI compared to the pericardial fluid of non ischemic patients. In conclusion, myocardial infarction reactivates an embryonic program in epicardial c-kit(+) cells; soluble factors released in the pericardial fluids following myocardial necrosis may play a role in this process. (c) 2009 Elsevier Ltd. All rights reserved.