DOI QR코드

DOI QR Code

Triglyceride Down-regulates Expression of MSR-1 in PMA-induced THP-1 Macrophages

  • Jung, Byung Chul (Department of Nutritional Sciences and Toxicology, University of California) ;
  • Kim, Sung Hoon (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University) ;
  • Woo, Sung-Hun (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University) ;
  • Lim, Jaewon (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University) ;
  • Kim, Yoon Suk (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University)
  • 투고 : 2020.07.21
  • 심사 : 2020.08.26
  • 발행 : 2020.09.30

초록

Atherosclerosis is a cardiovascular disease in which plaque builds up inside of an artery and can lead to various complications such as myocardial infarction, stroke, and thrombosis. Recently, hypertriglyceridemia has attracted significant attention as contributors to development of atherosclerosis. However, molecular mechanism of its contribution to atherosclerosis is poorly understood. Here we proposed a potential link between triglyceride (TG) and atherosclerosis. TG treatment promoted downregulation of certain scavenger receptor, macrophage scavenger receptor-1 (MSR-1) in phorbol myristate acetate (PMA)-derived human macrophages. TG treatment caused reduction of MSR-1 mRNA expression in a time- and dose-dependent manner. Using chemical inhibitors, we found that inhibition of signaling pathways associated with PI3K and PLC enhances TG-induced reduction of MSR-1 expression in THP-1 macrophages implying that PI3K and PLC is implicated in the expression of MSR-1 in macrophages. Since MSR-1 is associated with uptake and clearance of atherogenic lipoprotein, oxidized low density lipoprotein (oxi-LDL), our data suggest that increase of oxi-LDL due to TG-mediated reduction of its receptor MSR-1 can promote atherosclerosis.

키워드

참고문헌

  1. Aronis A, Madar Z, Tirosh O. Mechanism underlying oxidative stress-mediated lipotoxicity: Exposure of j774.2 macrophages to triacylglycerols facilitates mitochondrial reactive oxygen species production and cellular necrosis. Free Radic Biol Med. 2005. 38: 1221-1230. https://doi.org/10.1016/j.freeradbiomed.2005.01.015
  2. Carmena R, Duriez P, Fruchart JC. Atherogenic lipoprotein particles in atherosclerosis. Circulation. 2004. 109: III2-7.
  3. Chin JH, Azhar S, Hoffman BB. Inactivation of endothelial derived relaxing factor by oxidized lipoproteins. J Clin Invest. 1992. 89: 10-18. https://doi.org/10.1172/JCI115549
  4. de Winther MP, Gijbels MJ, van Dijk KW, van Gorp PJ, suzuki H, Kodama T, Frants RR, Havekes LM, Hofker MH. Scavenger receptor deficiency leads to more complex atherosclerotic lesions in apoe3leiden transgenic mice. Atherosclerosis. 1999. 144: 315-321. https://doi.org/10.1016/S0021-9150(98)00332-3
  5. Griffin EE, Ullery JC, Cox BE, Jerome WG. Aggregated ldl and lipid dispersions induce lysosomal cholesteryl ester accumulation in macrophage foam cells. J Lipid Res. 2005. 46: 2052-2060. https://doi.org/10.1194/jlr.M500059-JLR200
  6. Heier C, Kuhnlein RP. Triacylglycerol metabolism in drosophila melanogaster. Genetics. 2018. 210: 1163-1184. https://doi.org/10.1534/genetics.118.301583
  7. Kolodgie FD, Narula J, Burke AP, Haider N, Farb A, Hui-Liang Y, Smialek J, Virmani R. Localization of apoptotic macrophages at the site of plaque rupture in sudden coronary death. Am J Pathol. 2000. 157: 1259-1268. https://doi.org/10.1016/S0002-9440(10)64641-X
  8. Kunjathoor VV, Febbraio M, Podrez EA, Moore KJ, Andersson L, Koehn S, Rhee JS, Silverstein R, Hoff HF, Freeman MW. Scavenger receptors class a-i/ii and cd36 are the principal receptors responsible for the uptake of modified low density lipoprotein leading to lipid loading in macrophages. J Biol Chem. 2002. 277: 49982-49988. https://doi.org/10.1074/jbc.M209649200
  9. Lee MH, Kim SH, Ryu SR, Lee P, Moon C. Enhancing the effects of zerumbone on thp-1 cell activation. Korean J Clin Lab Sci. 2017. 49: 1-7. https://doi.org/10.15324/kjcls.2017.49.1.1
  10. Menet R, Bernard M, ElAli A. Hyperlipidemia in stroke pathobiology and therapy: Insights and perspectives. Front Physiol. 2018. 9: 488. https://doi.org/10.3389/fphys.2018.00488
  11. Rader DJ, Pure E. Lipoproteins, macrophage function, and atherosclerosis: Beyond the foam cell? Cell Metab. 2005. 1: 223-230. https://doi.org/10.1016/j.cmet.2005.03.005
  12. Ross R. The pathogenesis of atherosclerosis: A perspective for the 1990s. 1993.
  13. Suzuki H, Kurihara Y, Takeya M, Kamada N, Kataoka M, Jishage K, Ueda O, Sakaguchi H, Higashi T, Suzuki T, Takashima Y, Kawabe Y, Cynshi O, Wada Y, Honda M, Kurihara H, Aburatani H, Doi T, Matsumoto A, Azuma S, et al. A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection. Nature. 1997. 386: 292-296. https://doi.org/10.1038/386292a0
  14. Toth PP, Philip S, Hull M, Granowitz C. Association of elevated triglycerides with increased cardiovascular risk and direct costs in statin-treated patients. Mayo Clin Proc. 2019. 94: 1670-1680. https://doi.org/10.1016/j.mayocp.2019.03.028
  15. Whitman SC, Rateri DL, Szilvassy SJ, Cornicelli JA, Daugherty A. Macrophage-specific expression of class a scavenger receptors in ldl receptor (-/-) mice decreases atherosclerosis and changes spleen morphology. J Lipid Res. 2002. 43: 1201-1208. https://doi.org/10.1194/jlr.m200116-jlr200
  16. Witztum JL. Susceptibility of low-density lipoprotein to oxidative modification. Am J Med. 1993. 94: 347-349. https://doi.org/10.1016/0002-9343(93)90143-D
  17. Yu K, Park S, Chang Y, Hwang D, Kim G, Kim J, Kim S, Kim EJ, Lee D. Evaluation of commercial complementary DNA synthesis kits for detecting human papillomavirus. Korean J Clin Lab Sci. 2019. 51: 309-315. https://doi.org/10.15324/kjcls.2019.51.3.309