Department of Cardiology, Chest Hospital, Tianjin University, 300222 Tianjin, China.
Clinical School of Thoracic, Tianjin Medical University, 300222 Tianjin, China.
Front Biosci (Landmark Ed). 2023 Sep 25;28(9):223. doi: 10.31083/j.fbl2809223.
Macrophages expressing CC chemokine receptor 2 (CCR2) possess characteristics and performance akin to M1 polarized macrophages, which promote inflammation. Advanced heart failure (HF) patients with higher abundance of CCR2+ macrophages are more likely to experience adverse remodeling. The precise mechanism of CCR2+ macrophages in how they affect the progression of dilated cardiomyopathy remains unknown.
Cardiac biopsy samples from dilated cardiomyopathy patients (DCM) were used for immunohistochemistry and immunofluorescence staining. PCR is employed to identify the , , , , , , , , , , , , , , and mRNA expression of CCR2+ monocytes/macrophages from the peripheral blood of DCM patients. Seahorse was used to evaluate the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) of CCR2+ monocytes/macrophages. 2-DG was used to simulate a lack of glucose. Lentivirus containing GLUT1 inhibitory sequence was used to knockdown GLUT1 gene expression of CCR2+ monocytes/macrophages. Western Blot and immunofluorescence staining was used to evaluate the expression of NLRP3.
Immunostaining results of cardiac biopsy tissue from dilated cardiomyopathy (DCM) patients demonstrated that the progression to HF was associated with an increase in the number of CCR2+ macrophages. PCR results demonstrated that CCR2 monocytes and macrophages derived from the blood of DCM patients expressed elevated levels of inflammatory factors and up regulation of glycolysis related genes. In addition, OCR and glucose uptake experiments confirmed that increased glucose uptake of these cells was associated with greater inflammation and correlated with a worsening of cardiac function. limiting the glucose supply to CCR2+ monocytes and macrophages, or suppressing the activity of glucose transporter 1 (GLUT1) could reduce inflammation levels.
These results suggest that CCR2+ monocytes and macrophages rely on metabolic reprogramming to trigger inflammatory response and contribute to myocardial injury and the progression of DCM.
表达CC趋化因子受体2（CCR2）的巨噬细胞具有与M1极化巨噬细胞相似的特征和功能，可促进炎症反应。CCR2+巨噬细胞丰度较高的晚期心力衰竭（HF）患者更易发生不良重塑。CCR2+巨噬细胞影响扩张型心肌病进展的确切机制尚不清楚。
采用扩张型心肌病患者（DCM）的心脏活检样本进行免疫组织化学和免疫荧光染色。运用PCR鉴定DCM患者外周血中CCR2+单核细胞/巨噬细胞的 、 、 、 、 、 、 、 、 、 、 、 、 及 mRNA表达。使用海马分析仪评估CCR2+单核细胞/巨噬细胞的氧消耗率（OCR）和细胞外酸化率（ECAR）。用2-脱氧葡萄糖模拟葡萄糖缺乏。使用含GLUT1抑制序列的慢病毒敲低CCR2+单核细胞/巨噬细胞的GLUT1基因表达。采用蛋白质免疫印迹法和免疫荧光染色评估NLRP3的表达。
扩张型心肌病（DCM）患者心脏活检组织的免疫染色结果表明，向HF进展与CCR2+巨噬细胞数量增加有关。PCR结果表明，源自DCM患者血液的CCR2单核细胞和巨噬细胞表达升高的炎症因子水平以及糖酵解相关基因的上调。此外，OCR和葡萄糖摄取实验证实，这些细胞葡萄糖摄取增加与更严重的炎症相关，并与心脏功能恶化相关。限制CCR2+单核细胞和巨噬细胞的葡萄糖供应，或抑制葡萄糖转运蛋白1（GLUT1）的活性可降低炎症水平。
这些结果表明，CCR2+单核细胞和巨噬细胞依靠代谢重编程触发炎症反应，并导致心肌损伤和DCM进展。
