Department of Cardiology, Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, China.
Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases.
Bioengineered. 2021 Dec;12(2):10971-10981. doi: 10.1080/21655979.2021.2001924.
Macrophage infiltration is a hallmark pathological change observed in early stage myocardial ischemia/reperfusion (MI/R) injury and one of the main causes of myocardial damage. Here, we investigated the effects of p-Coumaric acid (p-CA) on macrophage polarization following MI/R injury and its mechanisms. , p-CA decreases the expression of LPS/IFN-γ-induced M1 macrophage markers (TNF-α, IL-6, iNOS and CCL2) and increases IL-4-induced M2 macrophage markers (IL-10, CD206, Arg1 and Mrc) in mouse bone marrow-derived macrophages (BMDMs). Additionally, p-CA elevated indoleamine 2, 3-dioxygenase (IDO) protein expression levels, M2 macrophage polarization and M2 macrophage markers through IL-4. In contrast, repression of IDO attenuated p-CA functions regulating BMDMs through IL-4. , IDO expression was downregulated in mouse hearts subjected to MI/R injury. Treatment of p-CA increased IDO expression in the hearts of MI/R mice. Functionally, p-CA decreases M1 macrophage markers, the number of M1 macrophages and inflammation around heart tissue following MI/R injury. Importantly, p-CA reduces cardiomyocyte apoptosis caused by MI/R. Altogether, our study identified that p-CA modulates macrophage polarization by promoting IDO expression and that p-CA attenuates macrophage-mediated inflammation following MI/R by promoting M2 macrophage polarization through IDO.
巨噬细胞浸润是早期心肌缺血/再灌注（MI/R）损伤中观察到的标志性病理变化之一，也是心肌损伤的主要原因之一。在这里，我们研究了 p-香豆酸（p-CA）对 MI/R 损伤后巨噬细胞极化的影响及其机制。结果表明，p-CA 降低了 LPS/IFN-γ 诱导的 M1 巨噬细胞标志物（TNF-α、IL-6、iNOS 和 CCL2）的表达，并增加了 IL-4 诱导的 M2 巨噬细胞标志物（IL-10、CD206、Arg1 和 Mrc）在小鼠骨髓来源的巨噬细胞（BMDMs）中。此外，p-CA 通过 IL-4 升高吲哚胺 2,3-双加氧酶（IDO）蛋白表达水平、M2 巨噬细胞极化和 M2 巨噬细胞标志物。相比之下，IDO 的抑制减弱了 p-CA 通过 IL-4 调节 BMDMs 的功能。进一步研究表明，IDO 在 MI/R 损伤的小鼠心脏中表达下调。p-CA 处理增加了 MI/R 小鼠心脏中的 IDO 表达。功能上，p-CA 降低了 MI/R 损伤后 M1 巨噬细胞标志物、M1 巨噬细胞数量和心脏组织周围的炎症。重要的是，p-CA 减少了 MI/R 引起的心肌细胞凋亡。总之，我们的研究表明，p-CA 通过促进 IDO 表达来调节巨噬细胞极化，并且 p-CA 通过 IDO 促进 M2 巨噬细胞极化来减轻 MI/R 后的巨噬细胞介导的炎症。
