Original articles

Toll-like receptor 4 regulates the inflammation induced by lipids in smooth muscle cells

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  • 1. Institute of Cardiovascular Disease, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;
    2. Department of Cardiology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;
    3. Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China

Received date: 2017-06-20

  Online published: 2017-10-25

Abstract

Objective: To investigate the mechanism of TLR4 in mediating the oxLDL-induced inflammation in smooth muscle cells (SMCs). Methods: TLR4 knockout mice and wild type C57BL/6 mice were randomly divided into control group (normal diet) and study group (high-fat diet) with 6 mice per group. Progression of atheroma was analyzed after 12 weeks in TLR4 knockout mice and wild type C57BL/6 mice. Primary SMCs of TLR4 knockout mice were cultured in vitro, and SMCs of wild type C57BL/6 were served as controls. SMCs were treated with oxLDL to induce inflammation, then TLR4 antibody was used to block TLR4 activity, and oxLDL-induced inflammation was compared between TLR4 knockout mice and wild type C57BL/6 mice. Results: High-fat diet could promote the expression of inflammatory cytokines in wild type C57BL/6 mice, but in TLR4 knockout mice there was no significant difference between the normal and high-fat diet groups. Moreover, blocking the activity of TLR4 could inhibit the oxLDL-induced inflammation in primary SMCs. Conclusions: TLR4 plays a role in regulating the oxLDL-induced inflammation in SMCs.

Cite this article

WANG Yanping, CHEN Yuanyuan, WU Liping, CHEN Yafen, YANG Ke, LIU Yan . Toll-like receptor 4 regulates the inflammation induced by lipids in smooth muscle cells[J]. Journal of Diagnostics Concepts & Practice, 2017 , 16(05) : 504 -509 . DOI: 10.16150/j.1671-2870.2017.05.010

References

[1] Kawai T, Akira S.TLR signaling[J]. Cell Death Differ,2006,13(5):816-825.
[2] Libby P, Ridker PM, Hansson GK.Progress and challenges in translating the biology of atherosclerosis[J]. Nature,2011,473(7347):317-325.
[3] Ross R.Atherosclerosis is an inflammatory disease[J]. Am Heart J,1999,138(5 Pt 2):S419-S420.
[4] Tabas I, García-Cardeña G, Owens GK.Recent insights into the cellular biology of atherosclerosis[J]. J Cell Biol,2015,209(1):13-22.
[5] 许旭光, 张延斌, 孙刘莎, 等. 辛伐他汀通过抑制TLR4信号通路调节血管平滑肌细胞炎症因子的表达[J]. 中国动脉硬化杂志,2014,22(12):1220-1224.
[6] 查晴, 曹丽娟, 王燕萍, 等. oxLDL通过TLR4诱导脂质累积和炎症反应促进动脉粥样硬化的分子机制[J]. 上海交通大学学报(医学版),2017,37(5):611-615.
[7] Albanese I, Daskalopoulou SS, Yu B, et al.The Urotensin Ⅱ System and Carotid Atherosclerosis: A Role in Vascular Calcification[J]. Front Pharmacol,2016,7:149.
[8] Alexander MR, Owens GK.Epigenetic control of smooth muscle cell differentiation and phenotypic switching in vascular development and disease[J]. Annu Rev Physiol,2012,74:13-40.
[9] Yoshida T, Yamashita M, Horimai C, et al.Smooth muscle-selective inhibition of nuclear factor-κB attenuates smooth muscle phenotypic switching and neointima formation following vascular injury[J]. J Am Heart Assoc,2013,2(3):e000230.
[10] Brand K, Page S, Rogler G, et al.Activated transcription factor nuclear factor-kappa B is present in the atherosclerotic lesion[J]. J Clin Invest,1996,97(7):1715-1722.
[11] Landry DB, Couper LL, Bryant SR, et al.Activation of the NF-kappa B and I kappa B system in smooth muscle cells after rat arterial injury. Induction of vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1[J]. Am J Pathol,1997,151(4):1085-1095.
[12] Bennett MR, Sinha S, Owens GK.Vascular Smooth Muscle Cells in Atherosclerosis[J]. Circ Res,2016,118(4):692-702.
[13] Vengrenyuk Y, Nishi H, Long X, et al.Cholesterol loadi-ng reprograms the microRNA-143/145-myocardin axis to convert aortic smooth muscle cells to a dysfunctional macrophage-like phenotype[J]. Arterioscler Thromb Vasc Biol,2015,35(3):535-546.
[14] Kiyan Y, Tkachuk S, Hilfiker-Kleiner D, et al.oxLDL induces inflammatory responses in vascular smooth muscle cells via urokinase receptor association with CD36 and TLR4[J]. J Mol Cell Cardiol,2014,66:72-82.
[15] Frantz S, Ertl G, Bauersachs J.Mechanisms of disease: Toll-like receptors in cardiovascular disease[J]. Nat Clin Pract Cardiovasc Med,2007,4(8):444-454.
[16] Gay NJ, Symmons MF, Gangloff M, et al.Assembly and localization of Toll-like receptor signalling complexes[J]. Nat Rev Immunol,2014,14(8):546-558.
[17] Yang K, Wang X, Liu Z, et al.Oxidized low-density lipoprotein promotes macrophage lipid accumulation via the toll-like receptor 4-Src pathway[J]. Circ J,2015,79(11):2509-2516.
[18] Yang K, Zhang XJ, Cao LJ, et al.Toll-like receptor 4 mediates inflammatory cytokine secretion in smooth muscle cells induced by oxidized low-density lipoprotein[J]. PLoS One,2014,9(4):e95935.
[19] Michelsen KS, Wong MH, Shah PK, et al.Lack of Toll-like receptor 4 or myeloid differentiation factor 88 reduces atherosclerosis and alters plaque phenotype in mice deficient in apolipoprotein E[J]. Proc Natl Acad Sci U S A,2004,101(29):10679-10684.
[20] Bae YS, Lee JH, Choi SH, et al.Macrophages generate reactive oxygen species in response to minimally oxidized low-density lipoprotein: toll-like receptor 4- and spleen tyrosine kinase-dependent activation of NADPH oxidase 2[J]. Circ Res,2009,104(2):210-218.
[21] Howell KW, Meng X, Fullerton DA, et al.Toll-like receptor 4 mediates oxidized LDL-induced macrophage differentiation to foam cells[J]. J Surg Res,2011,171(1):e27-e31.
[22] Miller YI, Viriyakosol S, Binder CJ, et al.Minimally modified LDL binds to CD14, induces macrophage spreading via TLR4/MD-2, and inhibits phagocytosis of apoptotic cells[J]. J Biol Chem,2003,278(3):1561-1568.
[23] Higashimori M, Tatro JB, Moore KJ, et al.Role of toll-like receptor 4 in intimal foam cell accumulation in apolipoprotein E-deficient mice[J]. Arterioscler Thromb Vasc Biol,2011,31(1):50-57.
[24] Methe H, Kim JO, Kofler S, et al.Expansion of circula-ting Toll-like receptor 4-positive monocytes in patients with acute coronary syndrome[J]. Circulation,2005,111(20):2654-2661.
[25] Xu XH, Shah PK, Faure E, et al.Toll-like receptor-4 is expressed by macrophages in murine and human lipid-rich atherosclerotic plaques and upregulated by oxidized LDL[J]. Circulation,2001,104(25):3103-3108.
[26] Yang K, He YS, Wang XQ, et al.MiR-146a inhibits oxidized low-density lipoprotein-induced lipid accumulation and inflammatory response via targeting toll-like receptor 4[J]. FEBS Lett,2011,585(6):854-860.
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