ETS1–THBS1 Axis Regulates Macrophage Polarization and Exacerbates Myocardial Injury in Diabetic Cardiomyopathy

作者：Xinbin Wang, Guligena Sawuer, Cheng Liang, Lu Lu, Gang Wu · 发表于：Journal of Cardiovascular Pharmacology · 年份：2025 · DOI：10.1097/fjc.0000000000001720 · 被引用次数：3 · 研究领域：Cardiovascular Function and Risk Factors、Cardiac Structural Anomalies and Repair、Cardiac tumors and thrombi

ABSTRACT: Diabetic cardiomyopathy is a major complication of diabetes marked by myocardial dysfunction, inflammation, and fibrosis. Immune cell infiltration and macrophage polarization are critical in diabetic cardiomyopathy progression. This study examined the role of thrombospondin-1 (THBS1) and its upstream regulatory mechanism, particularly focusing on the transcription factor ETS1, in diabetic myocardial injury. Using an streptozotocin-induced diabetic rat model, we observed significantly elevated THBS1 expression in the myocardium, accompanied by increased M1 macrophage infiltration and myocardial injury markers. Specific inhibition of THBS1 using shRNA lentiviral vectors significantly alleviated myocardial injury, reduced M1 macrophage polarization, and improved cardiac function. In addition, ETS1 was identified as a transcriptional regulator of THBS1, and its knockdown resulted in decreased THBS1 expression, further reducing myocardial inflammation and fibrosis. In vitro, ETS1 knockdown in high glucose-treated H9C2 cells reduced THBS1 expression, cell injury, and fibrosis-related marker expression. These findings demonstrate that the ETS1-THBS1 axis contributes to diabetic myocardial injury by promoting M1 macrophage polarization and fibrosis. Targeting this axis may uncover a novel regimen for alleviating myocardial damage in diabetic patients.