髓系细胞表达的触发受体-2通过PI3K/AKT途径促进心肌缺血损伤后心肌细胞的存活。
Triggering receptor expressed on myeloid cells-2 promotes survival of cardiomyocytes after myocardial ischemic injury through PI3K/AKT pathway.
作者信息
Fu Cong, Xu Qiancheng, Liu Jichun, Tang Shengxing, Liu Can, Cao Yuhan
机构信息
Department of Cardiology, Yi Ji Shan Hospital Affiliated to Wan Nan Medical College, Wuhu, China.
Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution (Wan Nan Medical College), Wuhu, China.
出版信息
Cardiovasc Diagn Ther. 2022 Feb;12(1):24-36. doi: 10.21037/cdt-21-490.
BACKGROUND
Previous studies have already revealed that triggering receptor expressed on myeloid cells-2 (TREM2) plays a significant protective role during the pathogenesis of ischemia injury in both brain and liver. This study aims to investigate the effect of TREM2 in myocardial ischemic injury.
METHODS
The mice myocardial infarction (MI) model was established via left anterior descending coronary artery ligation. TREM2 expression was examined with RT-PCR and Western blot. Whereafter, mice were randomly divided into control, sham, MI, Ad.TREM2 transfection group and Ad.Null transfection group. Recombinant adenovirus containing the gene coding full-length mouse TREM2 and EGFP (Ad.TREM2) or control vector containing gene only (Ad.Null) were immediately intramyocardial injected after left anterior descending ligated. After 7 days of MI, HE, Masson and TUNEL staining were performed to find the myocardial injury, infarcted size and cell apoptosis. Besides, echocardiography was performed to determine cardiac function. In addition, Western blot was performed to check the activity of PI3K/AKT signaling pathway in myocardial tissue. Furthermore, the plasma concentrations of TREM2 in 19 coronary artery disease (CAD) patients and 8 healthy controls were measured.
RESULTS
Compared with the sham group, TREM2 expression was significantly up-regulated in cardiac tissue in mice with MI. Cardiac tissue in mice transfected with Ad.TREM2 was demonstrated with alleviated injury, reduced infarct size, and decreased number of apoptotic cells. Echocardiography revealed that heart function was significantly improved in Ad.TREM2 transfection mice. Also, TREM2 transfection significantly activated the phosphorylation of AKT. At last, the plasma concentration of TREM2 was significantly elevated in patients with CAD and correlated with the severity of CAD.
CONCLUSIONS
TREM2 may curb myocardial ischemia injury via activating PI3K/AKT signal pathway. Besides, plasma TREM2 may be treated as a potential biomarker in the diagnosis of CAD to reflect the severity of coronary stenosis.
背景
既往研究已表明，髓系细胞触发受体2（TREM2）在脑和肝脏缺血性损伤发病机制中发挥重要保护作用。本研究旨在探讨TREM2在心肌缺血性损伤中的作用。
方法
通过结扎左冠状动脉前降支建立小鼠心肌梗死（MI）模型。采用RT-PCR和蛋白质免疫印迹法检测TREM2表达。之后，将小鼠随机分为对照组、假手术组、MI组、Ad.TREM2转染组和Ad.Null转染组。在左冠状动脉前降支结扎后立即心肌内注射含编码全长小鼠TREM2基因和EGFP的重组腺病毒（Ad.TREM2）或仅含基因的对照载体（Ad.Null）。MI后7天，进行苏木精-伊红（HE）、Masson和TUNEL染色以观察心肌损伤、梗死面积和细胞凋亡情况。此外，进行超声心动图检查以测定心功能。另外，采用蛋白质免疫印迹法检测心肌组织中PI3K/AKT信号通路的活性。此外，测定19例冠心病（CAD）患者和8例健康对照者血浆中TREM2浓度。
结果
与假手术组相比，MI小鼠心脏组织中TREM2表达显著上调。Ad.TREM2转染小鼠的心脏组织损伤减轻、梗死面积减小、凋亡细胞数量减少。超声心动图显示，Ad.TREM2转染小鼠的心功能显著改善。此外，TREM2转染显著激活了AKT的磷酸化。最后，CAD患者血浆中TREM2浓度显著升高，且与CAD严重程度相关。
结论
TREM2可能通过激活PI3K/AKT信号通路抑制心肌缺血性损伤。此外，血浆TREM2可作为CAD诊断的潜在生物标志物，以反映冠状动脉狭窄的严重程度。
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