来自 HIV+ 个体的功能失调的高密度脂蛋白在体外促进单核细胞来源的泡沫细胞形成。
Dysfunctional high-density lipoprotein from HIV+ individuals promotes monocyte-derived foam cell formation in vitro.
机构信息
aCentre for Biomedical Research, Burnet Institute bDepartment of Infectious Diseases, Monash University, Melbourne, Victoria, Australia cChildren's Hospital Oakland Research Institute, Oakland dUniversity of California, Los Angeles, Los Angeles, California, USA. *Thomas A. Angelovich, Anna C. Hearps, Anthony Jaworowski, and Theodoros Kelesidis contributed equally to this article.
出版信息
AIDS. 2017 Nov 13;31(17):2331-2336. doi: 10.1097/QAD.0000000000001642.
OBJECTIVE
The role of high-density lipoprotein (HDL) function in HIV-related atherosclerotic cardiovascular disease (CVD) is unclear. HDLs isolated from HIV [HIV(+)HDL] and HIV-uninfected individuals [HIV(-)HDL] were assessed for HDL function and ability to promote monocyte-derived foam cell formation (MDFCF; a key event in HIV-related CVD) ex vivo.
DESIGN/METHODS: Using an established in-vitro model of atherogenesis and plasma samples from an established cross-sectional study of virologically suppressed HIV men on stable effective antiretroviral therapy and with low CVD risk (median age: 42 years; n = 10), we explored the impact of native HDL [HIV(+)HDL] on MDFCF. In this exploratory study, we selected HIV(+)HDL known to be dysfunctional based on two independent measures of impaired HDL function: antioxidant (high HDLox) ability of HDL to release apolipoprotein A-I (ApoA-I) (low HDL-ApoA-I exchange). Five healthy men matched by age and race to the HIV group were included. Given that oxidation of HDL leads to abnormal HDL function, we also compared proatherogenic effects of HIV(+)HDL vs. chemically derived HDLox. The ex-vivo atherogenesis assay was performed using lipoproteins (purchased or isolated from plasma using ultracentrifugation) and monocytes purified via negative selection from healthy donors.
RESULTS
HIV(+)HDL known to have reduced antioxidant function and rate of HDL/ApoAI exchange promoted MDFCF to a greater extent than HDL (33.0 vs. 26.2% foam cells; P = 0.015). HDL oxidized in vitro also enhanced foam cell formation as compared with nonoxidized HDL (P < 0.01).
CONCLUSION
Dysfunctional HDL in virologically suppressed HIV individuals may potentiate atherosclerosis in HIV infection by promoting MDFCF.The role of HDL function in HIV-related atherosclerotic CVD is unclear. HDL isolated from HIV [HIV(+)HDL] and HIV-uninfected individuals [HIV(-)HDL] were assessed for HDL function and ability to promote foam cell formation ex vivo. HIV(+)HDL known to have reduced antioxidant function and rate of HDL/ApoA1 exchange promoted MDFCF to a greater extent than HDL(-)HDL (33.0 vs. 26.2% foam cells.Subject codes: Inflammation, Lipids and Cholesterol, Vascular Biology, Oxidant Stress, Atherosclerosis.
目的
高密度脂蛋白（HDL）功能在 HIV 相关动脉粥样硬化性心血管疾病（CVD）中的作用尚不清楚。从 HIV 阳性（HIV(+)）个体和 HIV 阴性个体中分离的 HDL（HIV(+)HDL 和 HIV(-)HDL）用于评估 HDL 功能以及促进单核细胞来源的泡沫细胞形成（MDFCF；HIV 相关 CVD 的关键事件）的能力。
设计/方法：使用体外动脉粥样硬化形成模型和经过病毒学抑制的 HIV 男性稳定有效抗逆转录病毒治疗且 CVD 风险较低（中位年龄：42 岁；n = 10）的横断面研究中的血浆样本，我们探讨了天然 HDL [HIV(+)HDL] 对 MDFCF 的影响。在这项探索性研究中，我们选择了根据两种独立的 HDL 功能受损测量来确定的功能失调的 HIV(+)HDL：HDL 释放载脂蛋白 A-I（ApoA-I）的抗氧化（高 HDLox）能力（低 HDL-ApoA-I 交换）。选择了 5 名年龄和种族与 HIV 组匹配的健康男性。由于 HDL 的氧化会导致异常的 HDL 功能，我们还比较了 HIV(+)HDL 与化学衍生的 HDLox 的促动脉粥样硬化作用。使用脂蛋白（通过超速离心从血浆中购买或分离）和通过阴性选择从健康供体中纯化的单核细胞进行体外动脉粥样形成测定。
结果
具有降低的抗氧化功能和 HDL/ApoAI 交换率的已知功能失调的 HIV(+)HDL 促进 MDFCF 的程度大于 HDL（33.0%与 26.2%泡沫细胞；P = 0.015）。与未氧化的 HDL 相比，体外氧化的 HDL 也增强了泡沫细胞的形成（P < 0.01）。
结论
病毒学抑制的 HIV 个体中功能失调的 HDL 可能通过促进 MDFCF 来增强 HIV 感染中的动脉粥样硬化。在 HIV 相关动脉粥样硬化性 CVD 中，HDL 功能的作用尚不清楚。从 HIV [HIV(+)HDL]和未感染 HIV 的个体 [HIV(-)HDL]中分离出的 HDL 用于评估其功能以及促进泡沫细胞形成的能力。已知具有降低的抗氧化功能和 HDL/ApoA1 交换率的 HIV(+)HDL 比 HDL(-)HDL 更能促进 MDFCF 的形成（33.0%与 26.2%泡沫细胞；P = 0.015）。
Zotero 插件