第三军医大学Liang-peng Li等研究人员合作发现，趋化因子CCL2通过激活JNK/STAT3轴促进心肌梗死小鼠的心脏再生和修复。该研究于2023年12月12日在线发表于国际一流学术期刊《中国药理学报》。

研究人员探讨了CCL2在心脏再生中的作用及其内在机制。通过永久结扎左前降支动脉诱导成年小鼠心肌梗死，研究人员发现心肌梗死小鼠血清和心脏组织中的CCL2水平显著升高。手术后立即心肌内注射重组CCL2（rCCL2，1 μg）可明显促进心肌细胞增殖，提高存活率和心功能，并缩小心肌梗死后小鼠的瘢痕大小。除了这些有益作用外，研究人员还观察到心肌梗死后小鼠的血管生成增加，心肌细胞凋亡减少。相反，用选择性CCL2合成抑制剂 Bindarit（30 μM）处理P1新生大鼠心室肌细胞（NRVM）可抑制CCL2的表达和心肌细胞的增殖。

研究人员在NRVM中证明，CCL2通过STAT3信号刺激心肌细胞增殖：用rCCL2（100 ng/mL）处理可显著提高STAT3的磷酸化水平，而STAT3磷酸化抑制剂Stattic（30 μM）可抑制rCCL2诱导的心肌细胞增殖。总之，这项研究表明，CCL2可通过激活STAT3信号促进心脏再生，这突出了它作为一种治疗剂治疗心肌缺血和相关心力衰竭的潜力。

据了解，刺激成体心肌细胞增殖是治疗心肌梗死（MI）的一种前景广阔的策略。早期的研究表明，心肌梗死患者和小鼠模型血浆和心脏组织中的CCL2水平均有所升高。

附：英文原文

Title: Chemokine CCL2 promotes cardiac regeneration and repair in myocardial infarction mice via activation of the JNK/STAT3 axis

Author: Wang, Wei, Chen, Xiao-kang, Zhou, Lu, Wang, Feng, He, Yan-ji, Lu, Bing-jun, Hu, Ze-gang, Li, Zhu-xin, Xia, Xue-wei, Wang, Wei Eric, Zeng, Chun-yu, Li, Liang-peng

Issue&Volume: 2023-12-12

Abstract: Stimulation of adult cardiomyocyte proliferation is a promising strategy for treating myocardial infarction (MI). Earlier studies have shown increased CCL2 levels in plasma and cardiac tissue both in MI patients and mouse models. In present study we investigated the role of CCL2 in cardiac regeneration and the underlying mechanisms. MI was induced in adult mice by permanent ligation of the left anterior descending artery, we showed that the serum and cardiac CCL2 levels were significantly increased in MI mice. Intramyocardial injection of recombinant CCL2 (rCCL2, 1μg) immediately after the surgery significantly promoted cardiomyocyte proliferation, improved survival rate and cardiac function, and diminished scar sizes in post-MI mice. Alongside these beneficial effects, we observed an increased angiogenesis and decreased cardiomyocyte apoptosis in post-MI mice. Conversely, treatment with a selective CCL2 synthesis inhibitor Bindarit (30μM) suppressed both CCL2 expression and cardiomyocyte proliferation in P1 neonatal rat ventricle myocytes (NRVMs). We demonstrated in NRVMs that the CCL2 stimulated cardiomyocyte proliferation through STAT3 signaling: treatment with rCCL2 (100ng/mL) significantly increased the phosphorylation levels of STAT3, whereas a STAT3 phosphorylation inhibitor Stattic (30μM) suppressed rCCL2-induced cardiomyocyte proliferation. In conclusion, this study suggests that CCL2 promotes cardiac regeneration via activation of STAT3 signaling, underscoring its potential as a therapeutic agent for managing MI and associated heart failure.

DOI: 10.1038/s41401-023-01198-0

Source: https://www.nature.com/articles/s41401-023-01198-0