Myoblast transplantation improves cardiac function after myocardial infarction through attenuating inflammatory responses.
Myoblast transplantation improves cardiac function after myocardial infarction through attenuating inflammatory responses.
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成肌细胞移植通过减弱炎症反应改善心肌梗死后的心功能
DOI：
10.18632/oncotarget.18244
复制
发表时间：
2017-09-15
期刊：
影响因子：
--
通讯作者：
Liu Z
中科院分区：
文献类型：
--
作者：
Wang B;Zhang L;Cao H;Yang J;Wu M;Ma Y;Fan H;Zhan Z;Liu Z
心肌梗死（MI）是一种非常常见的心脏急症，它导致不良的心脏重构，然后加重进行性心力衰竭。MI后心肌组织的炎症反应是心肌修复和伤口愈合所必需的。然而，过度炎症也是随后心力衰竭病理学的关键组成部分。成肌细胞移植在心肌梗死后心脏修复中已取得了令人瞩目的效果，但其并发症及其机制尚未完全阐明。在此，我们发现，人成肌细胞移植到小型猪心肌中，减少了心肌梗死后小型猪心肌组织中炎性细胞的浸润，降低了许多促炎基因的表达水平，并激活了炎症相关信号通路，同时上调了抗炎基因如IL-10的表达水平，这有助于改善心功能，缩小梗死面积，减轻心肌纤维化。此外，人成肌细胞共培养可抑制HMGB 1和HSP 60等损伤相关分子模式诱导的人THP-1细胞IL-1β和TNF-α的产生以及MAPK和NF-κB信号通路的激活，这可能与IL-10的产生上调有关。这些结果表明，成肌细胞移植通过抑制炎症反应改善心肌梗死后心脏损伤和心功能，为成肌细胞移植治疗心肌梗死提供了新的机制。
Myocardial infarction (MI) is a highly prevalent cardiac emergency, which results in adverse cardiac remodeling and then exacerbates progressive heart failure. Inflammatory responses in cardiac tissue after MI is necessary for myocardium repair and wound healing. However, the excessive inflammation is also a key component of subsequent heart failure pathology. Myoblast transplantation after MI have been fulfilled attractive effects on cardiac repair, but the complications of transplantation and the underlying mechanisms have not been fully elucidated. Here, we found that human myoblast transplantation into minipig myocardium decreased the infiltration of inflammatory cells, the expression levels of many pro-inflammatory genes and the activation of inflammation-related signal pathways, while upregulated the expression levels of anti-inflammatory genes such as IL-10 in cardiac tissue of minipig post-MI, which was contributed to the improved cardiac function, the decreased infarct area and the attenuated myocardial fibrosis. Moreover, co-culture of human myoblasts inhibited the production of IL-1β and TNF-α as well as activation of MAPK and NF-κB signaling pathway induced by damage-associated molecular patterns such as HMGB1 and HSP60 in human THP-1 cells, which was partially attributed to the up-regulated production of IL-10. Collectively, these results indicate that myoblast transplantation ameliorates heart injury and improves cardiac function post-MI through inhibiting the inflammatory response, which provides the novel mechanism for myoblast transplantation therapy of MI.
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