Liu Yuna, Gong Jinlin, Wang Qing, Wei Na, Zhao Lei, Wu Zhenan
Department of Clinical Laboratory, Beijing Hospital of Integrated Traditional Chinese and Western Medicine, No. 3 Yongding Road East Street, Beijing, 100039 People's Republic of China.
Department of Medical Technology Support, Jingxi Medical District, Chinese PLA General Hospital, Beijing, 100097 People's Republic of China.
Cytotechnology. 2024 Apr;76(2):167-178. doi: 10.1007/s10616-023-00606-x. Epub 2023 Dec 11.
Atherosclerosis constitutes a proverbial pathogenic mechanism for cardio-cerebrovascular disease that accounts for the most common cause of disability and morbidity for human health worldwide. Endothelial dysfunction and inflammation are the key contributors to the progression of atherosclerosis. Glutaredoxin 2 (GLRX2) is abundantly existed in various tissues and possesses a range of pleiotropic efficacy including anti-oxidative and anti-inflammatory responses. However, its role in atherosclerosis is still undefined. Here, down-regulation of GLRX2 was validated in lipopolysaccha (LPS)-induced vascular endothelial cells (HUVECs). Moreover, elevation of GLRX2 reversed the inhibition of cell viability in LPS-treated HUVECs and decreased LPS-induced increases in cell apoptosis and caspase-3 activity. Additionally, enhancement of GLRX2 expression antagonized oxidative stress in HUVECs under LPS exposure by inhibiting ROS, lactate dehydrogenase and malondialdehyde production and increased activity of anti-oxidative stress superoxide dismutase. Notably, GLRX2 abrogated LPS-evoked transcripts and releases of pro-inflammatory cytokine (TNF-α, IL-6, and IL-1β), chemokine MCP-1 and adhesion molecule ICAM-1 expression. Furthermore, the activation of Nrf2/HO-1 signaling was demonstrated in LPS-stimulated HUVECs. Importantly, blockage of the Nrf2 pathway counteracted the protective roles of GLRX2 in LPS-triggered endothelial cell injury, oxidative stress and inflammatory response. Thus, these data reveal that GLRX2 may alleviate the progression of atherosclerosis by regulating vascular endothelial dysfunction and inflammation via the activation of the Nrf2 signaling, supporting a promising therapeutic approach for atherosclerosis and its complications.
The online version contains supplementary material available at 10.1007/s10616-023-00606-x.
动脉粥样硬化是心脑血管疾病众所周知的致病机制，是全球人类健康中导致残疾和发病的最常见原因。内皮功能障碍和炎症是动脉粥样硬化进展的关键因素。谷氧还蛋白2（GLRX2）在各种组织中大量存在，并具有一系列多效性作用，包括抗氧化和抗炎反应。然而，其在动脉粥样硬化中的作用仍不明确。在此，在脂多糖（LPS）诱导的血管内皮细胞（HUVECs）中验证了GLRX2的下调。此外，GLRX2的升高逆转了LPS处理的HUVECs中细胞活力的抑制，并降低了LPS诱导的细胞凋亡增加和半胱天冬酶-3活性。此外，GLRX2表达的增强通过抑制活性氧、乳酸脱氢酶和丙二醛的产生，拮抗了LPS暴露下HUVECs中的氧化应激，并增加了抗氧化应激超氧化物歧化酶的活性。值得注意的是，GLRX2消除了LPS诱发的促炎细胞因子（TNF-α、IL-6和IL-1β）、趋化因子MCP-1和黏附分子ICAM-1的转录和释放。此外，在LPS刺激的HUVECs中证实了Nrf2/HO-1信号通路的激活。重要的是，Nrf2通路的阻断抵消了GLRX2在LPS触发的内皮细胞损伤、氧化应激和炎症反应中的保护作用。因此，这些数据表明，GLRX2可能通过激活Nrf2信号通路调节血管内皮功能障碍和炎症，从而减轻动脉粥样硬化的进展，为动脉粥样硬化及其并发症提供了一种有前景的治疗方法。
在线版本包含可在10.1007/s10616-023-00606-x获取的补充材料。
