Molecular and Cellular Biochemistry

, Volume 399, Issue 1–2, pp 123–130 | Cite as

MicroRNA-126 attenuates palmitate-induced apoptosis by targeting TRAF7 in HUVECs

  • Yi Wang
  • Feng Wang
  • Yan Wu
  • Li Zuo
  • Sumei Zhang
  • Qing Zhou
  • Wei Wei
  • Yuan Wang
  • Huaqing Zhu


The aim of the present study was to explore the role of miR-126 in palmitate-induced HUVECs apoptosis and the possible mechanisms. Palmitate inhibited miR-126 expression in HUVECs, increased reactive oxygen species (ROS) production, and induced apoptosis as determined by up-regulation of caspase-3 activity and DNA fragmentation. Overexpression of miR-126 decreased ROS production, TNF-α expression, and apoptosis in palmitate-stimulated HUVECs. In contrast, miR-126 antagomir enhanced palmitate-induced ROS production, TNF-α expression, and apoptosis. The induction of miR-126 correlated with a reduction in TRAF7. We further showed that miR-126 targeted and inhibited TRAF7 expression through target sites located in the 3′ untranslated region of TRAF7 mRNA. In concordance, miR-126 mimic reduced TRAF7 protein in HUVECs, whereas the inhibition of miR-126 increased it. This study demonstrates an anti-apoptotic role of miR-126 in HUVECs and identifies TRAF7 as a direct target of miR-126 in HUVECs.


miR-126 Palmitate ROS production TRAF7 Apoptosis 



This study was supported by the National Natural Science Foundation of China (No. 81070232, 81270372, 81470568), Key Project of Chinese Ministry of Education (No. 212077), Grants for Scientific Research of BSKY (No. XJ201107, XJ2008015) from Anhui Medical University.


  1. 1.
    Tanasescu M, Cho E, Manson J et al (2004) Dietary fat and cholesterol and the risk of cardiovascular disease among women with type 2 diabetes. Am J Clin Nutr 79:999–1005PubMedGoogle Scholar
  2. 2.
    Djoussé L, Benkeser D, Arnold A et al (2013) Plasma free fatty acids and risk of heart failure: the cardiovascular health study. Circ Heart Fail 6:964–969PubMedCrossRefGoogle Scholar
  3. 3.
    Jickling GC, Spence JD (2014) Free fatty acids to predict recurrent ischemic stroke. Neurology 82:1110–1111PubMedCrossRefGoogle Scholar
  4. 4.
    Caballero AE (2003) Endothelial dysfunction in obesity and insulin resistance: a road to diabetes and heart disease. Obes Res 11:1278–1289PubMedCrossRefGoogle Scholar
  5. 5.
    Gao X, Zhao XL, Zhu YH et al (2011) Tetramethylpyrazine protects palmitate-induced oxidative damage and mitochondrial dysfunction in C2C12 myotubes. Life Sci 88:803–809PubMedCrossRefGoogle Scholar
  6. 6.
    Liu K, Zhao W, Gao X et al (2012) Diosgenin ameliorates palmitate-induced endothelial dysfunction and insulin resistance via blocking IKKβ and IRS-1 pathways. Atherosclerosis 223:350–358PubMedCrossRefGoogle Scholar
  7. 7.
    Yamagishi S, Okamoto T, Amano S et al (2002) Palmitate-induced apoptosis of microvascular endothelial cells and pericytes. Mol Med 8:179–184PubMedCentralPubMedGoogle Scholar
  8. 8.
    Artwohl M, Roden M, Waldhausl W et al (2004) Free fatty acids trigger apoptosis and inhibit cell cycle progression in human vascular endothelial cells. FASEB J 18:146–148PubMedGoogle Scholar
  9. 9.
    Zhang M, Wang CM, Li J et al (2013) Berberine protects against palmitate-induced endothelial dysfunction: involvements of upregulation of AMPK and eNOS and downregulation of NOX4. Mediators Inflamm 2013:260–264Google Scholar
  10. 10.
    Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136:215–233PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Huntzinger E, Izaurralde E (2011) Gene silencing by microRNAs: contributions of translational repression and mRNA decay. Nat Rev Genet 12:99–110PubMedCrossRefGoogle Scholar
  12. 12.
    Winter J, Jung S, Keller S et al (2009) Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol 11:228–234PubMedCrossRefGoogle Scholar
  13. 13.
    Rayner KJ, Esau CC, Hussain FN et al (2011) Inhibition of mir-33a/b in non-human primates raises plasma hdl and lowers vldl triglycerides. Nature 2478:404–407CrossRefGoogle Scholar
  14. 14.
    Soh J, Iqbal J, Queiroz J et al (2013) MicroRNA-30c reduces hyperlipidemia and atherosclerosis in mice by decreasing lipid synthesis and lipoprotein secretion. Nat Med 19:892–900PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Loyer X, Potteaux S, Vion AC et al (2014) Inhibition of microRNA-92a prevents endothelial dysfunction and atherosclerosis in mice. Circ Res 31:434–443CrossRefGoogle Scholar
  16. 16.
    Wang S, Aurora AB, Johnson BA et al (2008) The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis. Dev Cell 15:261–271PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Fish JE, Santoro MM, Morton SU et al (2008) MiR-126 regulates angiogenic signaling and vascular integrity. Dev Cell 15:272–284PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Harris TA, Yamakuchi M, Ferlito M et al (2008) MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1. Proc Natl Acad Sci USA 105:1516–1521PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Bradley JR, Pober JS (2001) Tumor necrosis factor receptor-associated factors (TRAFs). Oncogene 44:6482–6491CrossRefGoogle Scholar
  20. 20.
    Wajant H, Henkler F, Scheurich P (2001) The TNF-receptor-associated factor family: scaffold molecules for cytokine receptors, kinases and their regulators. Cell Signal 6:389–400CrossRefGoogle Scholar
  21. 21.
    Xu LG, Li LY, Shu HB (2004) TRAF7 potentiates MEKK3-induced AP1 and CHOP activation and induces apoptosis. J Biol Chem 279:17278–17282PubMedCrossRefGoogle Scholar
  22. 22.
    Dimmeler S, Zeiher AM (2004) Vascular repair by circulating endothelial progenitor cells: the missing link in atherosclerosis? J Mol Med (Berl) 82:671–677CrossRefGoogle Scholar
  23. 23.
    Bonetti PO, Lerman LO, Lerman A (2003) Endothelial dysfunction: a marker of atherosclerotic risk. Arterioscler Thromb Vasc Biol 23:168–175PubMedCrossRefGoogle Scholar
  24. 24.
    Dimmeler S, Haendeler J, Zeiher AM (2002) Regulation of endothelial cell apoptosis in atherothrombosis. Curr Opin Lipidol 13:531–536PubMedCrossRefGoogle Scholar
  25. 25.
    Libby P, Ridker PM, Hansson GK (2011) Progress and challenges in translating the biology of atherosclerosis. Nature 473:317–325PubMedCrossRefGoogle Scholar
  26. 26.
    Weber C, Noels H (2011) Atherosclerosis: current pathogenesis and therapeutic options. Nat Med 17:1410–1422PubMedCrossRefGoogle Scholar
  27. 27.
    Tedgui A, Mallat Z (2003) Apoptosis, a major determinant of atherothrombosis. Arch Mal Coeur Vaiss 96:671–675PubMedGoogle Scholar
  28. 28.
    Zernecke A, Bidzhekov K, Noels H et al (2009) Delivery of microRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection. Sci Signal 2(100):ra81PubMedCrossRefGoogle Scholar
  29. 29.
    Higashi Y, Noma K, Yoshizumi M et al (2009) Endothelial function and oxidative stress in cardiovascular diseases. Circ J 73:411–418PubMedCrossRefGoogle Scholar
  30. 30.
    González-Flores D, Rodríguez AB, Pariente JA (2014) TNFa-induced apoptosis in human myeloid cell lines HL-60 and K562 is dependent of intracellular ROS generation. Mol Cell Biochem 390:281–287PubMedCrossRefGoogle Scholar
  31. 31.
    Kataoka H, Murakami R, Numaguchi Y (2010) Angiotensin II type 1 receptor blockers prevent tumor necrosis factor-alpha-mediated endothelial nitric oxide synthase reduction and superoxide production in human umbilical vein endothelial cells. Eur J Pharmacol 636:36–41PubMedCrossRefGoogle Scholar
  32. 32.
    Zhang H, Park Y, Wu J et al (2009) Role of TNF-alpha in vascular dysfunction. Clin Sci (Lond) 116:219–230CrossRefGoogle Scholar
  33. 33.
    Scudiero I, Zotti T, Ferravante A et al (2012) Tumor necrosis factor (TNF) receptor-associated factor 7 is required for TNF α-induced Jun NH2-terminal kinase activation and promotes cell death by regulating polyubiquitination and lysosomal degradation of c-FLIP protein. J Biol Chem 287:6053–6061PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Wang Z, Ruan Z, Mao Y et al (2014) MiR-27a is up regulated and promotes inflammatory response in sepsis. Cell Immunol 290:190–195PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Yi Wang
    • 1
    • 2
    • 3
  • Feng Wang
    • 2
  • Yan Wu
    • 2
    • 3
  • Li Zuo
    • 2
    • 3
  • Sumei Zhang
    • 2
    • 3
  • Qing Zhou
    • 2
  • Wei Wei
    • 1
  • Yuan Wang
    • 1
    • 2
    • 3
  • Huaqing Zhu
    • 1
    • 2
    • 3
  1. 1.Institute of Clinical PharmacologyAnhui Medical UniversityHefeiPeople’s Republic of China
  2. 2.Laboratory of Molecular Biology and Department of BiochemistryAnhui Medical UniversityHefeiPeople’s Republic of China
  3. 3.Key Laboratory of Gene Research of Anhui ProvinceHefeiPeople’s Republic of China

Personalised recommendations