Department of Cardiovascular Surgery, Xuzhou Cancer Hospital, Xuzhou, Jiangsu 221005, P.R. China.
Mol Med Rep. 2022 May;25(5). doi: 10.3892/mmr.2022.12678. Epub 2022 Mar 16.
Endothelial cells are an important component of the heart and vasculature and form a crucial link between the cardiovascular system and the immune system. Sestrin 1 (SESN1) has an important role in atherosclerosis by inhibiting NOD‑like receptor family pyrin domain containing 3 inflammasome activation. However, whether SESN1 is involved in human umbilical vein endothelial cell (HUVEC) injury caused by atherosclerosis has remained to be elucidated. The present study aimed to investigate the functions of SESN1 in the inflammatory response, apoptosis and endothelial‑mesenchymal transition (EndMT) of HUVECs following stimulation with oxidized low‑density lipoprotein (Ox‑LDL). SESN1 expression at the mRNA and protein levels was detected using reverse transcription‑quantitative PCR (RT‑qPCR) and western blot analysis. Following SESN1 overexpression in Ox‑LDL‑stimulated HUVECs, cell viability was determined using a Cell Counting Kit‑8 assay. Terminal deoxynucleotidyl transferase‑mediated nick‑end labeling staining was employed to detect cell apoptosis and western blot analysis was used to determine the levels of apoptosis‑related proteins. RT‑qPCR, ELISA and western blot were utilized to determine the levels of inflammatory factors. Immunofluorescence staining, RT‑qPCR and western blot analysis were employed to assess the EndMT of Ox‑LDL‑stimulated HUVECs. The results revealed that SESN1 exhibited a low expression in HUVECs following Ox‑LDL stimulation. SESN1 overexpression suppressed inflammation, apoptosis and EndMT in Ox‑LDL‑induced HUVECs. In addition, SESN1 stimulated adenosine monophosphate‑activated protein kinase catalytic subunit α1/sirtuin 1 signaling to suppress Ox‑LDL receptor‑1 expression. An AMPK and SIRT1 inhibitor reversed the effects of SESN1 overexpression on the inflammatory response, apoptosis and EndMT of HUVECs exposed to Ox‑LDL. Taken together, the present study demonstrated that SENS1 exerts a suppressive effect on Ox‑LDL‑induced inflammation, apoptosis and EndMT of HUVECs, suggesting that SENS1 may be used as a novel biomarker for endothelial injury‑related disorders.
内皮细胞是心脏和脉管系统的重要组成部分，它们在心血管系统和免疫系统之间形成了至关重要的联系。Sestrin1（SESN1）通过抑制 NOD 样受体家族富含吡咯域的 3 炎性小体的激活，在动脉粥样硬化中发挥重要作用。然而，SESN1 是否参与动脉粥样硬化引起的人脐静脉内皮细胞（HUVEC）损伤仍有待阐明。本研究旨在探讨 SESN1 在氧化低密度脂蛋白（Ox-LDL）刺激后的 HUVEC 炎症反应、细胞凋亡和内皮-间充质转化（EndMT）中的作用。采用逆转录-定量 PCR（RT-qPCR）和 Western blot 分析检测 SESN1 在 mRNA 和蛋白水平的表达。在 Ox-LDL 刺激的 HUVEC 中转染 SESN1 过表达载体后，通过细胞计数试剂盒-8 检测细胞活力。采用末端脱氧核苷酸转移酶介导的缺口末端标记染色检测细胞凋亡，Western blot 检测凋亡相关蛋白水平。采用 RT-qPCR、ELISA 和 Western blot 检测炎症因子水平。采用免疫荧光染色、RT-qPCR 和 Western blot 分析评估 Ox-LDL 刺激的 HUVEC 的 EndMT。结果显示，Ox-LDL 刺激后 HUVEC 中 SESN1 表达水平较低。SESN1 过表达抑制 Ox-LDL 诱导的 HUVEC 中的炎症、凋亡和 EndMT。此外，SESN1 刺激 AMPK 催化亚单位α1/沉默调节蛋白 1 信号通路抑制 Ox-LDL 受体-1 的表达。AMPK 和 SIRT1 抑制剂逆转了 SESN1 过表达对 Ox-LDL 诱导的 HUVEC 炎症反应、凋亡和 EndMT 的影响。综上所述，本研究表明 SESN1 对 Ox-LDL 诱导的 HUVEC 炎症、凋亡和 EndMT 具有抑制作用，提示 SESN1 可作为内皮损伤相关疾病的新型生物标志物。
