Li Jing, Wang Cong, Wang Wenjing, Liu Lingzi, Zhang Qingqing, Zhang Jun, Wang Bo, Wang Shujing, Hou Li, Gao Chuanzhou, Yu Xiao, Sun Lei
Department of Pathology and Forensic Medicine, College of Basic Medical Sciences, Dalian Medical University, Dalian, China.
Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Institute of Glycobiology, Dalian Medical University, Dalian, China.
Front Cardiovasc Med. 2021 Mar 11;8:624796. doi: 10.3389/fcvm.2021.624796. eCollection 2021.
Peroxiredoxin 2 (PRDX2), an inhibitor of reactive oxygen species (ROS), is potentially involved in the progression of atherosclerosis (AS). The aim of this study was to explore the role and mechanism of PRDX2 in AS. The expression of PRDX2 was evaluated in 14 human carotid artery tissues with or without AS. The results showed that the positive reaction of PRDX2 was observed in the carotid artery vascular smooth muscle cells (CAVSMCs). To assess the mechanism by which PRDX2 may function in AS, the CAVSMCs were transfected with pEX4-PRDX2 and si-PRDX2. The catalase, hydrogen peroxide (HO) scavenger, was used to further confirm that PRDX2-induced inhibitory effects might be mediated through reducing ROS levels. Phenotype alteration and functional testing included transcription testing, immunostaining, and expression studies. The drug of MAPK signaling pathway inhibitors SB203580, SP600125, and PD98059 was used to evaluate the underlying mechanism. In this study, we found that the protein level of PRDX2 and the level of HO were higher in the human AS carotid artery tissues than in the normal carotid artery tissues, accompanied with the activation of MAPK signaling pathway. The up-regulation of PRDX2 in the CAVSMCs significantly decreased the expression of ROS, collagen type I (COL I), collagen type III (COL III), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) and inhibited the proliferation, migration, and transformation of the CAVSMCs. The up-regulation of PRDX2 reversed the effect of the CAVSMCs treated with tumor necrosis factor-α (TNF-α). In addition, PRDX2 down-regulation promoted the protein levels of p-p38, p-JNK, and p-ERK, which was confirmed in relevant MAPK inhibitor treatment experiments. Our results suggest a protective role of PRDX2, as a scavenger of ROS, in AS progression through inhibiting the VSMC phenotype alteration and function MAPK signaling pathway.
过氧化物酶2（PRDX2）作为一种活性氧（ROS）抑制剂，可能参与动脉粥样硬化（AS）的进展。本研究旨在探讨PRDX2在AS中的作用及机制。评估了14例有或无AS的人颈动脉组织中PRDX2的表达。结果显示，在颈动脉血管平滑肌细胞（CAVSMC）中观察到PRDX2的阳性反应。为了评估PRDX2在AS中可能发挥作用的机制，用pEX4-PRDX2和si-PRDX2转染CAVSMC。用过氧化氢酶（一种过氧化氢（HO）清除剂）进一步证实PRDX2诱导的抑制作用可能是通过降低ROS水平介导的。表型改变和功能测试包括转录测试、免疫染色和表达研究。使用丝裂原活化蛋白激酶（MAPK）信号通路抑制剂SB203580、SP600125和PD98059来评估潜在机制。在本研究中，我们发现人AS颈动脉组织中PRDX2的蛋白水平和HO水平高于正常颈动脉组织，同时伴有MAPK信号通路的激活。CAVSMC中PRDX2的上调显著降低了ROS、I型胶原（COL I）、III型胶原（COL III）、血管细胞黏附分子-1（VCAM-1）和细胞间黏附分子-1（ICAM-1）的表达，并抑制了CAVSMC的增殖、迁移和转化。PRDX2的上调逆转了肿瘤坏死因子-α（TNF-α）处理的CAVSMC的效应。此外，PRDX2下调促进了p-p38、p-JNK和p-ERK的蛋白水平，这在相关的MAPK抑制剂处理实验中得到了证实。我们的结果表明，PRDX2作为一种ROS清除剂，通过抑制血管平滑肌细胞（VSMC）表型改变和功能以及MAPK信号通路，在AS进展中发挥保护作用。
