Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, No. 83, Wenhua Road, Shenhe District, Shenyang, Liaoning, China.
Department of Medicine & Therapeutics, and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong.
Oxid Med Cell Longev. 2022 Sep 1;2022:6248779. doi: 10.1155/2022/6248779. eCollection 2022.
Inflammation plays important roles during myocardial infarction (MI). Macrophage polarization is a major factor that drives the inflammatory process. Our previous study found that RNA polymerase II subunit 5-mediating protein (RMP) knockout in cardiomyocytes caused heart failure by impairing mitochondrial structure and function. However, whether macrophage RMP plays a role in MI has not been investigated.
Macrophage RMP-knockout in combination with a mouse model of MI was used to study the function of macrophage RMP in MI. Next, we modified bone marrow-derived macrophages (BMDMs) by plasmid transfection, and the BMDMs were administered to LysM-Cre/DTR mice by tail vein injection. Immunoblotting and immunofluorescence were used to detect macrophage polarization, fibrosis, angiogenesis, and the p38 signaling pathway in each group.
Macrophage RMP deficiency aggravates cardiac dysfunction, promotes M1 polarization, and inhibits angiogenesis after MI. However, RMP overexpression in macrophages promotes M2 polarization and angiogenesis after MI. Mechanistically, we found that RMP regulates macrophage polarization through the heat shock protein 90- (HSP90-) p38 signaling pathway.
Macrophage RMP plays a significant role in MI, likely by regulating macrophage polarization via the HSP90-p38 signaling pathway.
炎症在心肌梗死（MI）中起着重要作用。巨噬细胞极化是驱动炎症过程的主要因素。我们之前的研究发现，心肌细胞中 RNA 聚合酶 II 亚基 5 介导蛋白（RMP）的敲除通过损害线粒体结构和功能导致心力衰竭。然而，巨噬细胞 RMP 是否在 MI 中发挥作用尚未得到研究。
使用巨噬细胞 RMP 敲除与 MI 小鼠模型相结合的方法来研究巨噬细胞 RMP 在 MI 中的功能。接下来，我们通过质粒转染修饰骨髓来源的巨噬细胞（BMDMs），并通过尾静脉注射将 BMDMs 给予 LysM-Cre/DTR 小鼠。免疫印迹和免疫荧光用于检测各组中巨噬细胞极化、纤维化、血管生成和 p38 信号通路。
巨噬细胞 RMP 缺乏加重 MI 后的心脏功能障碍，促进 M1 极化，并抑制血管生成。然而，MI 后巨噬细胞中 RMP 的过表达促进 M2 极化和血管生成。机制上，我们发现 RMP 通过热休克蛋白 90-（HSP90-）p38 信号通路调节巨噬细胞极化。
巨噬细胞 RMP 在 MI 中起重要作用，可能通过 HSP90-p38 信号通路调节巨噬细胞极化。
