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首页> 外文期刊>Cellular Physiology and Biochemistry >Transient Receptor Potential Melastatin 4 (TRPM4) Contributes to High Salt Diet-Mediated Early-Stage Endothelial Injury
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Transient Receptor Potential Melastatin 4 (TRPM4) Contributes to High Salt Diet-Mediated Early-Stage Endothelial Injury

机译：瞬态受体潜在的melastatin 4（TRPM4）有助于高盐饮食介导的早期内皮损伤

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>Background/Aims: The present study investigated whether the transient receptor potential melastatin 4 (TRPM4) channel plays a role in high salt diet (HSD)-induced endothelial injuries. Methods: Western blotting and immunofluorescence were used to examine TRPM4 expression in the mesenteric endothelium of Dahl salt-sensitive (SS) rats fed a HSD. The MTT, TUNEL, and transwell assays were used to evaluate the cell viability, cell apoptosis, and cell migration, respectively, of human umbilical vein endothelial cells (HUVECs). Enzyme-linked immunosorbent assays were used to determine the concentrations of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion protein 1 (VCAM-1), and E-selectin. Carboxy-H2DCFDA, a membrane-permeable reactive oxygen species (ROS)-sensitive fluorescent probe, was used to detect intracellular ROS levels. Results: TRPM4 was mainly expressed near the plasma membrane of mesenteric artery endothelial cells, and its expression level increased in SS hypertensive rats fed a HSD. Its protein expression was significantly upregulated upon treatment with exogenous hydrogen peroxide (H2O2) and aldosterone in cultured HUVECs. Cell viability decreased upon treatment with both agents in a concentration-dependent manner, which could be partially reversed by 9-phenanthrol, a specific TRPM4 inhibitor. Exogenous H2O2 induced apoptosis, enhanced cell migration, and increased the release of adhesion molecules, including ICAM-1, VCAM-1, and E-selectin, all of which were significantly attenuated upon treatment with 9-phenanthrol. Aldosterone and H2O2 induced the accumulation of intracellular ROS, which was significantly inhibited by 9-phenanthrol, suggesting that oxidative stress is one of the mechanisms underlying aldosterone-induced endothelial injury. Conclusions: Given the fact that oxidative stress and high levels of circulating aldosterone are present in hypertensive patients, we suggest that the upregulation of TRPM4 in the vascular endothelium may be involved in endothelial injuries caused by these stimuli.
机译：> 背景/目的： 本研究调查了瞬时受体电位褪黑素4（TRPM4）通道是否在高盐饮食（HSD）诱导的内皮损伤中起作用。 方法： 采用蛋白质印迹法和免疫荧光法检测喂食HSD的Dahl盐敏感性（SS）大鼠肠系膜内皮中TRPM4的表达。使用MTT，TUNEL和transwell分析分别评估人脐静脉内皮细胞（HUVEC）的细胞活力，细胞凋亡和细胞迁移。酶联免疫吸附试验用于确定细胞间粘附分子1（ICAM-1），血管细胞粘附蛋白1（VCAM-1）和E-选择素的浓度。 Carboxy-H2DCFDA，一种膜渗透性活性氧（ROS）敏感的荧光探针，用于检测细胞内ROS的水平。 结果： TRPM4主要表达于肠系膜动脉内皮细胞的质膜附近，并且在喂食HSD的SS高血压大鼠中其表达水平升高。在培养的HUVEC中，外源过氧化氢（H 2 O 2 ）和醛固酮处理后，其蛋白表达明显上调。两种药物以浓度依赖的方式处理后，细胞活力都会下降，这可能会被9-菲咯啉（一种特定的TRPM4抑制剂）部分逆转。外源H 2 O 2 诱导细胞凋亡，增强细胞迁移并增加粘附分子（包括ICAM-1，VCAM-1和E-选择素）的释放。在用9-菲咯啉治疗后明显减弱。醛固酮和H 2 O 2 诱导细胞内ROS的积累，并被9-菲咯啉显着抑制，这表明氧化应激是醛固酮诱导内皮细胞形成的机制之一。受伤。 结论： 鉴于高血压患者存在氧化应激和高水平的循环醛固酮，我们建议血管内皮中TRPM4的上调可能与内皮有关这些刺激引起的伤害。

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