Mukhamedova Nigora, Rose Honor, Cui Huanhuan L, Grant Angela, Tchoua Urbain, Dart Anthony, Bukrinsky Michael, Sviridov Dmitri
BakerIDI Heart and Diabetes Institute, Melbourne, Australia.
Atherosclerosis. 2009 Oct;206(2):439-43. doi: 10.1016/j.atherosclerosis.2009.02.042. Epub 2009 Mar 21.
HIV infection is associated with elevated risk of cardiovascular disease. The effect of antiretroviral drugs on metabolism of atherogenic very low and low density lipoproteins is well studied, but a possible effect of these drugs on reverse cholesterol transport is still unclear. The objective of this study was to assess the effect of various classes of anti-HIV drugs on cellular cholesterol efflux.
The effect of pharmacological concentrations of seven commonly used antiretroviral compounds, Stavudine, Efavirenz, Nevirapine, Lopinavir, Amprenavir, Nelfinavir and Ritonavir, on cholesterol efflux from RAW 264.7 mouse macrophages and human monocyte-derived macrophages to apolipoprotein A-I and high density lipoprotein was tested.
At high pharmacological concentration Nelfinavir and Ritonavir inhibited cholesterol efflux, while other compounds had no effect. However, the same concentrations of Nelfinavir and Ritonovir induced apoptosis, suggesting that the effect of these compounds on cholesterol efflux most likely resulted from their cytotoxicity. When tested in non-cytotoxic concentrations, Nelfinavir and Ritonavir did not affect cholesterol efflux from RAW 264.7 cells, human monocyte-derived macrophages, or human macrophages infected with HIV-1.
We conclude that tested antiretroviral compounds do not have a specific effect on cholesterol efflux.
HIV感染与心血管疾病风险升高相关。抗逆转录病毒药物对致动脉粥样硬化的极低密度脂蛋白和低密度脂蛋白代谢的影响已得到充分研究，但这些药物对逆向胆固醇转运的潜在影响仍不清楚。本研究的目的是评估各类抗HIV药物对细胞胆固醇流出的影响。
测试了七种常用抗逆转录病毒化合物（司他夫定、依非韦伦、奈韦拉平、洛匹那韦、安普那韦、奈非那韦和利托那韦）的药理浓度对RAW 264.7小鼠巨噬细胞和人单核细胞衍生巨噬细胞向载脂蛋白A-I和高密度脂蛋白的胆固醇流出的影响。
在高药理浓度下，奈非那韦和利托那韦抑制胆固醇流出，而其他化合物无此作用。然而，相同浓度的奈非那韦和利托那韦诱导细胞凋亡，表明这些化合物对胆固醇流出的影响很可能是由其细胞毒性所致。当在无细胞毒性浓度下进行测试时，奈非那韦和利托那韦不影响RAW 264.7细胞、人单核细胞衍生巨噬细胞或感染HIV-1的人巨噬细胞的胆固醇流出。
我们得出结论，所测试的抗逆转录病毒化合物对胆固醇流出没有特异性影响。
