Department of Kinesiology and Applied Physiology, University of Delaware, Newark, Delaware, United States.
Department of Medical and Molecular Sciences, University of Delaware, Newark, Delaware, United States.
Am J Physiol Heart Circ Physiol. 2024 Jan 1;326(1):H110-H115. doi: 10.1152/ajpheart.00621.2023. Epub 2023 Nov 3.
Changes in endothelial function precede the development of cardiovascular disease (CVD). We have previously shown that age-related declines in endothelial function in women are due in part to a reduction in endothelial cell endothelin-B receptor (ETR) protein expression. However, it is not known if ETR protein expression changes with aging in men. The purpose of this study was to test the hypothesis that ETR protein expression is attenuated in older men (OM) compared with younger men (YM). Primary endothelial cells were harvested from the antecubital vein of 14 OM (60 ± 6 yr; 26 ± 3 kg/m) and 17 YM (24 ± 5 yr; 24 ± 2 kg/m). Cells were stained with 4',6-diamidino-2-phenylindole, vascular endothelial cadherin, and ETR. Images were quantified using immunocytochemistry. Endothelial function was assessed using brachial artery flow-mediated dilation (FMD). Systolic BP was similar (OM, 123 ± 11 vs. YM, 122 ± 10 mmHg) whereas diastolic BP was higher in OM (OM, 77 ± 7 vs. YM, 70 ± 6 mmHg; < 0.01). Total testosterone was lower in OM (OM, 6.28 ± 4.21 vs. YM, 9.10 ± 2.68 ng/mL; = 0.03). As expected, FMD was lower in OM (OM, 3.85 ± 1.51 vs. YM, 6.40 ± 2.68%; < 0.01). However, ETR protein expression was similar between OM and YM (OM, 0.39 ± 0.17 vs. YM, 0.42 ± 0.17 AU; = 0.66). These data suggest that ETR protein expression is not altered with age in men. These findings contrast with our previous data in women and further support sex differences in the endothelin system. Our laboratory has previously shown that age-related declines in endothelial function are associated with a reduction in endothelial cell ETR protein expression in women. However, it is unclear if endothelial cell ETR protein expression is reduced with aging in men. This study demonstrates that endothelial cell ETR protein expression is preserved with aging in men, and provides additional evidence for sex differences in the endothelin system.
内皮功能的变化先于心血管疾病 (CVD) 的发展。我们之前已经表明,女性内皮功能的衰老与内皮细胞内皮素-B 受体 (ETR) 蛋白表达的减少有关。然而,尚不清楚男性的 ETR 蛋白表达是否会随着年龄的增长而发生变化。本研究旨在验证以下假设:与年轻男性 (YM) 相比,老年男性 (OM) 的 ETR 蛋白表达减少。从 14 名 OM(60 ± 6 岁;26 ± 3 kg/m)和 17 名 YM(24 ± 5 岁;24 ± 2 kg/m)的肘前静脉中提取原代内皮细胞。用 4',6-二脒基-2-苯基吲哚、血管内皮钙黏蛋白和 ETR 对细胞进行染色。使用免疫细胞化学法对图像进行定量。使用肱动脉血流介导的扩张 (FMD) 评估内皮功能。收缩压相似(OM,123 ± 11 对 YM,122 ± 10 mmHg),而 OM 的舒张压较高(OM,77 ± 7 对 YM,70 ± 6 mmHg;<0.01)。OM 中的总睾酮水平较低(OM,6.28 ± 4.21 对 YM,9.10 ± 2.68 ng/mL;= 0.03)。正如预期的那样,OM 中的 FMD 较低(OM,3.85 ± 1.51 对 YM,6.40 ± 2.68%;<0.01)。然而,OM 和 YM 之间的 ETR 蛋白表达相似(OM,0.39 ± 0.17 对 YM,0.42 ± 0.17 AU;= 0.66)。这些数据表明,男性的 ETR 蛋白表达不会随年龄而改变。这些发现与我们之前在女性中的数据形成对比,进一步支持了内皮素系统中的性别差异。我们的实验室之前已经表明,与女性相比,与年龄相关的内皮功能下降与内皮细胞 ETR 蛋白表达减少有关。然而,尚不清楚男性的内皮细胞 ETR 蛋白表达是否会随年龄增长而减少。本研究表明,男性内皮细胞 ETR 蛋白表达随年龄增长而保持不变,为内皮素系统中的性别差异提供了更多证据。