The George Washington University, Washington, DC, USA.
Biochem Biophys Res Commun. 2012 Mar 2;419(1):95-8. doi: 10.1016/j.bbrc.2012.01.137. Epub 2012 Feb 4.
HIV-infected subjects are at high risk of developing atherosclerosis, in part due to virus-induced impairment of HDL metabolism. Here, using as a model of HIV infection the NOD.Cg-Prkdc(scid)IL2rg(tm1Wjl)/SzJ (NSG) mice humanized by human stem cell transplantation, we demonstrate that LXR agonist TO901317 potently reduces viral replication and prevents HIV-induced reduction of plasma HDL. These results establish that humanized mice can be used to investigate the mechanisms of HIV-induced impairment of HDL formation, a major feature of dyslipidemia associated with HIV-1 infection, and show potential benefits of developing LXR agonists for treatment of HIV-associated cardio-vascular disease.
HIV 感染的受试者发生动脉粥样硬化的风险很高，部分原因是病毒诱导的 HDL 代谢受损。在这里，我们使用 NOD.Cg-Prkdc(scid)IL2rg(tm1Wjl)/SzJ (NSG) 小鼠作为 HIV 感染的模型，该模型通过人类干细胞移植实现了人源化，我们证明了 LXR 激动剂 TO901317 能够有效地抑制病毒复制，并预防 HIV 诱导的血浆 HDL 减少。这些结果表明，人源化小鼠可用于研究 HIV 诱导的 HDL 形成受损的机制，这是与 HIV-1 感染相关的血脂异常的主要特征，并显示出开发 LXR 激动剂治疗 HIV 相关心血管疾病的潜力。
