PP2A alleviates oxidized LDL-induced endothelial dysfunction by regulating LOX-1/ROS/MAPK axis

被引:6
|
作者
Xu, Kaicheng [1 ]
Liu, Xiwen [2 ]
Yin, Dexin [2 ]
Ren, Guanghao [2 ]
Zhao, Yue [2 ]
机构
[1] Jilin Univ, Dept Anesthesiol, China Japan Union Hosp, Changchun 130033, Jilin, Peoples R China
[2] Jilin Univ, Dept Vasc Surg, China Japan Union Hosp, Changchun 130033, Jilin, Peoples R China
关键词
PP2A; Atherosclerosis; Dysfunction; LOX-1/ROS/MAPK axis; LOX-1; EXPRESSION; OXLDL UPTAKE; TNF-ALPHA; CELLS; ATHEROSCLEROSIS; ROS; PROMOTES; INACTIVATION; ACTIVATION; PATHWAY;
D O I
10.1016/j.lfs.2020.117270
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Aims: The purpose of this study is to investigate the effect of PP2A on the progression of AS and the special molecular mechanism. Main methods: The expression of PP2A in Human umbilical vein endothelial cells (HUVECs) induced by different concentrations of Ox-LDL was measured by RT-PCR and Western blot. The binding activity of PP2A and LOX-1 was determined by CoIP assay. Western blot was used to measure the protein expression of VCAM-1, ICAM-1 and MCP-1. Key finding: The results revealed that the expression of PP2A was decreased with the increase of Ox-LDL concentration in HUVECs. Overexpression of PP2A alleviated Ox-LDL-induced dysfunction and inflammatory response in HUVECs. The results of Co-immunoprecipitation (CoIP) showed that PP2A had direct effect on LOX-1, and PP2A inhibited the expression of LOX-1. In addition, overexpression of LOX-1 reversed the inhibitory effect of PP2A on Ox-LDL-induced dysfunction and inflammatory response in HUVECs. What is more, PP2A inhibited LOX-1/ROS/MAPK axis. Significance: it suggests that PP2A alleviates Ox-LDL-induced dysfunction and inflammatory response of HUVECs potentially by regulating the LOX-1/ROS/MAPK axis,which suggests that PP2A has anti-inflammatory effect during the formation of as, and the molecular therapy of PP2A provides a theoretical basis.
引用
收藏
页数:7
相关论文
共 50 条
  • [21] Trichosanatine alleviates oxidized low-density lipoprotein induced endothelial cells injury via inhibiting the LOX-1/p38 MAPK pathway
    Zhang, Lei
    Jia, Yu-Hua
    Zhao, Xiao-Shan
    Zhou, Feng-Hua
    Pan, Yun-Yun
    Wan, Qiang
    Cui, Xiao-Bing
    Sun, Xue-Gang
    Chen, Yu-Yao
    Zhang, Yu
    Cheng, Sai-Bo
    AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH, 2016, 8 (12): : 5455 - 5464
  • [22] Oxidized LDL through LOX-1 modulates LDL-receptor expression in human coronary artery endothelial cells
    Hu, B
    Li, DY
    Sawamura, T
    Mehta, JL
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2003, 307 (04) : 1008 - 1012
  • [23] The neurokinin-1 receptor antagonist aprepitant ameliorates oxidized LDL-induced endothelial dysfunction via KLF2
    Zheng, Jianghua
    Chen, Kai
    Zhu, Yanbin
    Wang, Haifei
    Chen, Zhilong
    Yong, Xi
    Yin, Hongshun
    Chen, Jingquan
    Lai, Kun
    Liu, Yujuan
    MOLECULAR IMMUNOLOGY, 2019, 106 : 29 - 35
  • [24] Membrane type matrix metalloproteinase-1 (MT1-MMP) is a cell surface modifier of RhoA/Rac1-mediated signaling pathways and forms a complex with LOX-1 in oxidized LDL-induced endothelial dysfunction
    Sugimoto, K.
    Ishibashi, T.
    Sawamura, T.
    Kamioka, M.
    Uekita, H.
    Ohkawara, H.
    Inoue, N.
    Takuwa, Y.
    Teramoto, T.
    Takeishi, Y.
    EUROPEAN HEART JOURNAL, 2009, 30 : 727 - 727
  • [25] Formononetin Alleviates the Inflammatory Response Induced by Carotid Balloon Injury in Rats via the PP2A/MAPK Axis
    Zhao, Huanli
    Wu, Xuejun
    Yang, Shumeng
    Jiang, Lili
    Yu, Huiying
    Li, Yubin
    IMMUNOLOGICAL INVESTIGATIONS, 2025,
  • [26] LOX-1 mediates lysophosphatidylcholine-induced oxidized LDL uptake in smooth muscle cells
    Aoyama, T
    Chen, MY
    Fujiwara, H
    Masaki, T
    Sawamura, T
    FEBS LETTERS, 2000, 467 (2-3) : 217 - 220
  • [27] Antisense directed at endothelial oxidized LDL receptor LOX-1 inhibits apoptosis in human coronary artery endothelial cells
    Mehta, JL
    Li, D
    JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2000, 35 (02) : 295A - 295A
  • [28] Oxidized LDL receptor LOX-1 is involved in rat zymosan-induced arthritis.
    Sawamura, T
    Nakagawa, T
    Kakinuma, T
    Nakamura, T
    Masaki, T
    JOURNAL OF PHARMACOLOGICAL SCIENCES, 2003, 91 : 108P - 108P
  • [29] Minimally oxidized LDL induced ERK1/2 activation via homodimerization of Lox-1 in the cell membrane
    Tanigawa, H
    Miura, SI
    Uehara, Y
    Zhang, B
    Matsuo, Y
    Fujino, M
    CIRCULATION, 2004, 110 (17) : 198 - 198
  • [30] EGCG and quercetin attenuate oxidized LDL-induced endothelial apoptosis via differential MAPK-responsive pathways
    Choi, J. S.
    Choi, Y. J.
    Kang, S. W.
    Bae, J. Y.
    Kang, Y. H.
    JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2007, 42 : S82 - S82