Highly Up-Regulation of Fas Ligand Gene Expression after Increasing in Oxidized Low-Density Lipoprotein

Year 2025, , 54 - 57, 15.01.2025

Burcu Bayyurt , Serdal Arslan

https://doi.org/10.34248/bsengineering.1578992

Abstract

Oxidized low-density lipoprotein (ox-LDL) shows many harmful effects such as induction of apoptosis on function of endothelial cell (EC). Fas ligand (FASL) induces apoptosis in divergent pathological conditions. EC apoptosis which induced by ox-LDL is related with FASL. In this study, we aimed to determine how different ox-LDL levels affect FASL expression in ECs. We treated human umbilical vein endothelial cells (HUVECs) with two different concentration of ox-LDL. FASL gene expression in groups was detected by quantitative polymerase chain reaction (qPCR). We compared FASL gene expression level between the groups according to ∆∆Ct method. FASL gene expression was statistic significantly up-regulated in the group treated higher amounts of ox-LDL (P<0.001). We found that treatment with higher amounts of ox-LDL in HUVECs increased FASL gene expression dramatically. According to our findings, we concluded that increasing the amount of ox-LDL may be critical in inducing the FASL-dependent apoptotic pathway in ECs.

Keywords

Oxidized low-density lipoprotein, Fas ligand, Gene expression, Quantitative polymerase chain reaction, Human umbilical vein endothelial cell

Ethical Statement

Ethics committee approval was not required for this study because of there was no study on animals or humans.

Thanks

HUVEC and ox-LDL that were used in cell line experiments had been provided from consumables left over from projects by Sivas Cumhuriyet University Scientific Research Unit and Scientific Research and Technological Research Council of Türkiye, respectively.

References

• Cao X, Yang J, He L, Liu C. 2024. Circ_0005699 Expedites ox-LDL-Triggered endothelial cell injury via targeting miR-384/ASPH axis. Cardiovasc Toxicol, 24 (10): 1067-1076.
• Imanishi T, Hano T, Sawamura T, Takarada S, Nishio I. 2002. Oxidized low density lipoprotein potentiation of Fas-induced apoptosis through lectin-like oxidized-low density lipoprotein receptor-1 in human umbilical vascular endothelial cells. Circ J, 66 (11): 1060-1064.
• Khatana C, Saini NK, Chakrabarti S, Saini V, Sharma A, Saini RV, Saini AK. 2020. Mechanistic insights into the oxidized low-density lipoprotein-induced atherosclerosis. Oxid Med Cell Longev, 5245308.
• Li D, Yang B, Mehta JL. 1998. Ox-LDL induces apoptosis in human coronary artery endothelial cells: Role of PKC, PTK, bcl-2, and Fas. Am J Physiol, 275: H568-H576.
• Li HL, Wang AB, Zhang R, Wei YS, Chen HZ, She ZG, Huang Y, Liu DP, Liang CC. 2006. A20 inhibits oxidized low-density lipoprotein-induced apoptosis through negative Fas/Fas ligand-dependent activation of caspase-8 and mitochondrial pathways in murine RAW264.7 macrophages. Cell Physiol, 208: 307-18.
• Li Q, Wang Y, Li H, Shen G, Hu S. 2014. Ox-LDL influences peripheral Th17/Treg balance by modulating Treg apoptosis and Th17 proliferation in atherosclerotic cerebral infarction. Cell Physiol Biochem, 33(6): 1849-1862.
• Li X, Yang Y, Wang Z, Jiang S, Meng Y, Song X, Zhao L, Zou L, Li M, Yu T. 2021. Targeting non-coding RNAs in unstable atherosclerotic plaques: Mechanism, regulation, possibilities, and limitations. Int J Biol Sci, 17(13): 3413-3427.
• Liu Q, Liu Z, Zhou LJ, Cui YL, Xu JM. 2020. The long noncoding RNA NKILA protects against myocardial ischaemic injury by enhancing myocardin expression via suppressing the NF-κB signalling pathway. Exp Cell Res, 15; 387(2): 111774.
• Livak KJ, Schmittgen TD. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods, 25(4): 402-8.
• Ma J, Ling J, Tong R, Guo J, Zhu Z. 2024. siLOXL2 inhibits endothelial inflammatory response and EndMT induced by ox-LDL. Cerebrovasc Dis Extra, 14 (1): 165-176.
• Malarkannan S. 2020. Molecular mechanisms of FASL-mediated ‘reverse-signaling’. Mol Immunol, 127: 31-37.
• Munno M, Mallia A, Greco A, Modafferi G, Banfi C, Eligini S. 2024. Radical Oxygen species, oxidized low-density lipoproteins, and lectin-like oxidized low-density lipoprotein receptor 1: a vicious circle in atherosclerotic process. Antioxidants, 13 (5): 583.
• Poznyak AV, Nikiforov NG, Markin AM, Kashirskikh DA, Myasoedova VA, Gerasimova EV, Orekhov AN. 2021. Overview of OxLDL and its impact on cardiovascular health: focus on atherosclerosis. Front Pharmacolü 11: 613780.
• RT2 Profiler PCR Arrays & Assays Data Analysis Handbook. 2019. https://dataanalysis2.qiagen.com/static/templates/RT2_Profiler_PCR_Data_Analysis_Handbook_190930.pdf (accessed date: November 01, 2024).
• Sata M, Walsh K. 1998. Oxidized LDL activates Fas-mediated endothelial cell apoptosis. J Clin Invest, 102: 1682-1689.
• Tian H, Yao ST, Yang NN, Ren J, Jiao P, Zhang X, Qin SC. 2017. D4F alleviates macrophage-derived foam cell apoptosis by inhibiting the NF-κB-dependent Fas/FASL pathway. Sci Rep, 7(1): 7333.
• Wu MY, Li CJ, Hou MF, and Chu PY. 2017. New insights into the role of inflammation in the pathogenesis of atherosclerosis. Int J Mol Sci, 18 (10): 2034.