Wang Yan-Ge, Wang Ding-Hang, Wei Wen-Hui, Xiong Xin, Wu Jing-Jing, Han Zhan-Ying, Cheng Long-Xian
Department of Cardiology, First Affiliated Hospital of Zhengzhou University, No.1 Jianshe Dong Road, Zhengzhou, China.
Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Jie-Fang Avenue 1277#, Wuhan, China.
Mol Cell Biochem. 2025 Apr;480(4):2437-2454. doi: 10.1007/s11010-024-05112-y. Epub 2024 Sep 12.
The fundamental pathophysiological mechanism in the progression of chronic heart failure following acute myocardial infarction (AMI) is ventricular remodeling, in which innate and adaptive immunity both play critical roles. Myeloid-derived suppressor cells (MDSCs) have been demonstrated to function in a range of pathological conditions, such as infections, inflammation, autoimmune diseases, and tumors. However, it is unclear how MDSCs contribute to cardiac remodeling following AMI. This study aimed to identify the function and underlying mechanism of MDSCs in controlling cardiac remodeling following AMI. Following AMI in mice, MDSCs frequencies changed dynamically, considerably increased on day 7 in blood, spleens, lymph nodes and hearts, and decreased afterwards. Consistently, mice with AMI displayed enhanced cardiac function on day 14 post-AMI, reduced infract size and higher survival rates on day 28 post-AMI following the adoptive transfer of MDSCs. Furthermore, MDSCs inhibited the inflammatory response by decreasing pro-inflammatory cytokine (TNF-α, IL-17, Cxcl-1, and Cxcl-2) expression, up-regulating anti-inflammatory cytokine (TGF-β1, IL-10, IL-4, and IL-13) expression, reducing CD3 T cell infiltration in the infarcted heart and enhancing M2 macrophage polarization. Mechanistically, MDSCs improved the release of anti-inflammatory factors (TGF-β1 and IL-10) and decreased the injury of LPS-induced cardiomyocytes in vitro in a manner dependent on cell-cell contact. Importantly, blockade of IL-10 partially abolished the cardioprotective role of MDSCs. This study found that MDSCs contributed to the restoration of cardiac function and alleviation of adverse cardiac remodeling after AMI possibly by inhibiting inflammation.
急性心肌梗死（AMI）后慢性心力衰竭进展的基本病理生理机制是心室重构，其中固有免疫和适应性免疫均发挥关键作用。髓系来源的抑制细胞（MDSCs）已被证明在一系列病理状况中发挥作用，如感染、炎症、自身免疫性疾病和肿瘤。然而，尚不清楚MDSCs在AMI后如何促进心脏重构。本研究旨在确定MDSCs在控制AMI后心脏重构中的作用及潜在机制。小鼠发生AMI后，MDSCs频率动态变化，在第7天血液、脾脏、淋巴结和心脏中显著增加，随后下降。同样，AMI小鼠在接受MDSCs过继转移后，于AMI后第14天心脏功能增强，梗死面积减小，在AMI后第28天存活率更高。此外，MDSCs通过降低促炎细胞因子（TNF-α、IL-17、Cxcl-1和Cxcl-2）表达、上调抗炎细胞因子（TGF-β1、IL-10、IL-4和IL-13）表达、减少梗死心脏中CD3 T细胞浸润以及增强M2巨噬细胞极化来抑制炎症反应。机制上，MDSCs以细胞间接触依赖的方式改善抗炎因子（TGF-β1和IL-10）的释放，并在体外降低脂多糖诱导的心肌细胞损伤。重要的是，阻断IL-10部分消除了MDSCs的心脏保护作用。本研究发现，MDSCs可能通过抑制炎症促进AMI后心脏功能的恢复和不良心脏重构的减轻。
