2025年5月25日 周日
Home > Archive>Volume 29, Issue 1, 2021 >54-59
PDF HTML XML Export Cite reminder
Silencing of MAP4K4 alleviated ox-LDL-induced vascular endothelial cell injury via regulating PPARγ/ABCA1 signaling
Author:
Affiliation:

Department of Neurology, the First People’s Hospital of Zhengzhou, Zhengzhou, Henan 450004, China)

Clc Number:

R541

  • Article
    • | |
  • Metrics
    • |
  • Reference [22]
    • | | | |
  • Comments
    Abstract:

    Aim The purpose of the present study was to investigate the potential role and mechanism of mitogen activated protein kinase kinase kinase kinase 4 (MAP4K4) in human umbilical vein endothelial cell (HUVEC) injury induced by oxidized low density lipoprotein (ox-LDL). Methods The cell injury model was induced by ox-LDL (100 mg/L). The mRNA expression of MAP4K4 was detected using RT-PCR assay. Western blot analysis was conducted to estimate the protein levels of MAP4K4, Bax, Bcl-2, C-Caspase-3, peroxisome proliferators-activated receptorγ (PPARγ) and ATP binding cassette transporter A1 (ABCA1). CCK8 assay was performed to measure cell viability. ELISA assay was applied to analyse cell apoptosis. The reactive oxygen species (ROS) production was measured by DCFH-DA assay.The content of malondialdehyde(MDA) and the activity of superoxide dismutase (SOD) and catalase (CAT)were detected by commercially available assay kits. Results The expression of MAP4K4 was elevated in ox-LDL-stimulated HUVEC. In addition, silencing of MAP4K4 apparently enhanced cell viability and attenuated HUVEC apoptosis induced by ox-LDL accompanied by a decrease in the expression of Bax and C-Caspase-3 and an increase in the expression of Bcl-2. Moreover, MAP4K4 knockdown remarkably alleviated the generation of ROS and the content of MDA accompanied with the enhanced activity of anti-oxidative enzyme system SOD and CAT triggerd by ox-LDL. Mechanically, ablation of MAP4K4 obviously activated PPARγ/ABCA1 signaling pathway. Conclusion Depletion of MAP4K4 relieves ox-LDL-induced vascular endothelial injury by reducing apoptosis and mitigating oxidative damage via PPARγ/ABCA1 activation, thus providing the basis for the therapeutic effect of MAP4K4 on the As.

    Reference
    [1] Tabas I, Williams KJ, Borén J.Subendothelial lipoprotein retention as the initiating process in atherosclerosis:update and therapeutic implications.Circulation, 7,6(16):1832-1844.
    [2] Cao L, Zhang Z, Li Y, et al.LncRNA H19/miR-let-7 axis participates in the regulation of ox-LDL-induced endothelial cell injury via targeting periostin.Int Immunopharmacol, 9,2:496-503.
    [3] Itabe H.Oxidized low-density lipoprotein as a biomarker of in vivo oxidative stress:from atherosclerosis to periodontitis.J Clin Biochem Nutr, 2,1(1):1-8.
    [4] Yuan W, Chang HS, Liu X, et al.Brazilian green propolis inhibits ox-LDL-stimulated oxidative stress in human umbilical vein endothelial cell partly through PI3K/Akt/mTOR mediated Nrf2/HO-1 pathway.Evid-Based Compl Alt, 9,9:5789574.
    [5] Roth FR, Skoura A, Matevossian A, et al.Endothelial protein kinase MAP4K4 promotes vascular inflammation and atherosclerosis.Nat Commun, 5,6:8995.
    [6] Pannekoek WJ, Linnemann JR, Brouwer PM, et al.Rap1 and RAP2 antagonistically control endothelial barrier resistance.PLoS One, 3,8(2):e57903.
    [7] Mano T, Masuyama T, Yamamoto K, et al.Endothelial dysfunction in the early stage of atherosclerosis precedes appearance of intimal lesions assessable with intravascular ultrasound.Am Heart J, 6,1(2):231-238.
    [8] Gimbrone J, Garcia CG.Endothelial cell dysfunction and the pathobiology of atherosclerosis.Circ Res, 6,8(4):620-636.
    [9] Mallat Z, Tedgui A.Rate of apoptosis in human atherosclerosis.Am J Pathol, 8,3(4):1320-1321.
    [10] Chrissobolis S, Miller AA, Drummond GR, et al.Oxidative stress and endothelial dysfunction in cerebrovascular disease.Front Biosci (Landmark Ed), 1,6:1733-1745.
    [11] Husain K, Hernandez W, Ansari RA, et al.Inflammation, oxidative stress and renin angiotensin system in atherosclerosis.World J Biol Chem, 5,6(3):209-217.
    [12] Yang Q, Wang CY, Jin YE, et al.Disocin prevents postmenopausal atherosclerosis in ovariectomized LDLR－/－ mice through a PGC-1α/ERα pathway leading to promotion of autophagy and inhibition of oxidative stress, inflammation and apoptosis.Pharmacol Res, 9,8:104414.
    [13] Cominacini L, Pasini AF, Garbin U, et al.Oxidized low density lipoprotein (ox-LDL) binding to ox-LDL receptor-1 in endothelial cell induces the activation of NF-kappaB through an increased production of intracellular reactive oxygen species.J Biol Chem, 0,5(17):12633-12638.
    [14] Lin XL, Hu HJ, Liu YB, et al.Allicin induces the upregulation of ABCA1 expression via PPARγ/LXRα signaling in THP-1 macrophage-derived foam cell.Int J Mol Med, 7,9(6):1452-1460.
    [15] Lake NJ, Taylor RL, Trahair H, et al.TRAK2, a novel regulator of ABCA1 expression, cholesterol efflux and HDL biogenesis.Eur Heart J, 7,8(48):3579-3587.
    [16] Westerterp M, Bochem AE, Yvan-Charvet L, et al.ATP-binding cassette transporters, atherosclerosis, and inflammation.Circ Res, 4,4(1):157-170.
    [17] Tabet F, Remaley AT, Segaliny AI, et al.The 5a apolipoprotein A-I mimetic peptide displays antiinflammatory and antioxidant properties in vivo and in vitro.Arterioscler Thromb Vasc Biol, 0,0(2):246-252.
    [18] Liu D, Ding ZZ, Wu MZ, et al.The apolipoprotein A-I mimetic peptide, D-4F, alleviates ox-LDL-induced oxidative stress and promotes endothelial repair through the eNOS/HO-1 pathway.J Mol Cell Cardiol, 7,5:77-88.
    [19] Chawla A, Boisvert WA, Lee CH, et al.A PPAR gamma-LXR-ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis.Mol Cell, 1,7(1):161-171.
    [20] Ozasa H, Ayaori M, Iizuka M, et al.Pioglitazone enhances cholesterol efflux from macrophages by increasing ABCA1/ABCG1 expressions via PPARγ/LXRα pathway:findings from in vitro and ex vivo studies.Atherosclerosis, 1,9(1):141-150.
    [21] Gu HF, Li N, Xu ZQ, et al.Chronic unpredictable mild stress promotes atherosclerosis via HMGB1/TLR4-Mediated downregulation of PPARγ/LXRα/ABCA1 in ApoE－/－ mice.Front Physiol, 9,0:165.
    [22] Guntur KV, Guilherme A, Xue L, et al.MAP4K4 negatively regulates peroxisome proliferator-activated receptor (PPAR) gamma protein translation by suppressing the mammalian target of rapamycin (mTOR) signaling pathway in cultured adipocytes.J Biol Chem, 0,5(9):6595-6603.
    Related
    Cited by
    Comments
    Comments
    分享到微博
    Submit
Get Citation

WANG Yuxiang, YAN Yan, LI Yongfang, LI Aifan, LI Yanling. Silencing of MAP4K4 alleviated ox-LDL-induced vascular endothelial cell injury via regulating PPARγ/ABCA1 signaling[J]. Editorial Office of Chinese Journal of Arteriosclerosis,2021,29(1):54-59.

Copy
Share
Article Metrics
  • Abstract:676
  • PDF: 776
  • HTML: 0
  • Cited by: 0
History
  • Received:December 16,2019
  • Revised:March 03,2020
  • Online: January 22,2021
Article QR Code

You are the 48777 visitor

Post Code：421001 Fax：0734-8160523

Phone：0734-8160765 E-mail：dmzzbjb@163.net

Editorial Office of Chinese Journal of Arteriosclerosis ® 2025