Herbers Oliver, Höltke Carsten, Usai Marco Virgilio, Hochhalter Jana, Mallik Moushami, Wildgruber Moritz, Helfen Anne, Stölting Miriam
Clinic for Radiology, University Hospital Münster, 48149 Münster, Germany.
Department of Vascular Surgery, St. Franziskus Hospital, 48145 Münster, Germany.
Int J Mol Sci. 2025 Mar 5;26(5):2310. doi: 10.3390/ijms26052310.
Endothelin-1 (ET-1) levels are altered in atherosclerosis, while the roles of the endothelin receptors ETR and ETR during the pathogenesis of atherosclerosis remain unclear. Therefore, the focus of this study was to clarify how endothelin receptors are expressed in advanced human atherosclerotic plaques and how this is related to atherosclerotic risk factors. Ex vivo expression analysis was performed by quantitative real-time PCR (qRT-PCR) of 98 atherosclerotic plaques and controls that were obtained from adult patients undergoing vascular surgery. Correlation analyses of atherosclerosis-promoting factors were accomplished using a linear regression model. We found an overall reduced expression of ET receptors and smooth muscle actin (SMA), a marker of healthy vascular smooth muscle cells, in atherosclerotic plaques, whereas the levels of ET-1 and matrix metalloproteinase 2 (MMP-2), a marker of atherosclerosis progression, remained unchanged. Reduced expression was predominantly correlated with hypertension, which affects both receptors as well as SMA. Age, body mass index (BMI) and gender also correlated with either ETR, ETR or SMA expression in advanced plaques. In contrast, no effect of diabetes mellitus or smoking was found, indicating an ancillary effect of those risk factors. The results of our study indicate that endothelin receptor expression during the pathogenesis of atherosclerosis is predominantly correlated with hypertension.
内皮素-1（ET-1）水平在动脉粥样硬化中会发生改变，而内皮素受体ETR和ETR在动脉粥样硬化发病机制中的作用仍不清楚。因此，本研究的重点是阐明内皮素受体在晚期人类动脉粥样硬化斑块中的表达情况以及这与动脉粥样硬化危险因素的关系。通过对98个动脉粥样硬化斑块和从接受血管手术的成年患者获取的对照样本进行定量实时PCR（qRT-PCR），进行了体外表达分析。使用线性回归模型完成了对动脉粥样硬化促进因子的相关性分析。我们发现，在动脉粥样硬化斑块中，ET受体和健康血管平滑肌细胞标志物平滑肌肌动蛋白（SMA）的表达总体降低，而动脉粥样硬化进展标志物ET-1和基质金属蛋白酶2（MMP-2）的水平保持不变。表达降低主要与高血压相关，高血压会影响这两种受体以及SMA。年龄、体重指数（BMI）和性别也与晚期斑块中的ETR、ETR或SMA表达相关。相比之下，未发现糖尿病或吸烟的影响，表明这些危险因素具有辅助作用。我们的研究结果表明，动脉粥样硬化发病机制中的内皮素受体表达主要与高血压相关。
