High-density lipoprotein-mediated cholesterol efflux capacity is improved by treatment with antiretroviral therapy in acute human immunodeficiency virus infection.
High-density lipoprotein-mediated cholesterol efflux capacity is improved by treatment with antiretroviral therapy in acute human immunodeficiency virus infection.
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DOI：
10.1093/ofid/ofu108
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发表时间：
2014-12
影响因子：
4.2
通讯作者：
Grinspoon SK
中科院分区：
文献类型：
--
作者：
Lo J;Rosenberg ES;Fitzgerald ML;Bazner SB;Ihenachor EJ;Hawxhurst V;Borkowska AH;Wei J;Zimmerman CO;Burdo TH;Williams KC;Freeman MW;Grinspoon SK
感染人类免疫缺陷病毒（HIV）的个体具有降低的高密度脂蛋白（HDL）-胆固醇和增加的心血管疾病（CVD）。巨噬细胞的胆固醇逆向转运可能被HIV抑制，并导致CVD增加。人体研究尚未调查HIV和抗逆转录病毒治疗（ART）对胆固醇流出的纵向影响。 急性HIV感染的受试者被随机分配接受或不接受ART。胆固醇流出能力测定离体暴露后，小鼠巨噬细胞的载脂蛋白B耗竭患者血清在基线和12周后。 12周后，随机接受ART治疗的受试者中HIV RNA下降最多。现有的胆固醇数据表明，从接受ART治疗的受试者中获得的血清最能增加Abca 1 +/+巨噬细胞的外排能力（20.5% ± 5.0%至24.3% ± 6.9%，基线至12周，P = 0.007; ART组[n = 6] vs 18.0% ± 3.9%至19.1% ± 2.9%，基线至12周，P = 0.30;未治疗组[n = 6] [P = 0.04 ART vs未治疗组]）。HIV RNA的变化与Abca 1 +/+巨噬细胞胆固醇流出的变化呈负相关（r =-0.62，P = 0.03），在控制HDL-胆固醇、CD 4+细胞和单核细胞或巨噬细胞活化标志物的变化后，这一发现仍然显著（P = 0.03）。 在急性感染HIV的受试者中，随机接受ART的受试者的去载脂蛋白B血清随着时间的推移在更大程度上刺激ATP结合盒转运体A1介导的胆固醇外排。胆固醇外排能力的改善与病毒载量的降低独立相关。
Individuals infected with human immunodeficiency virus (HIV) have decreased high-density lipoprotein (HDL)-cholesterol and increased cardiovascular disease (CVD). Reverse cholesterol transport from macrophages may be inhibited by HIV and contribute to increased CVD. Human studies have not investigated longitudinal effects of HIV and antiretroviral therapy (ART) on cholesterol efflux. Subjects with acute HIV infection were randomized to ART or not. Cholesterol efflux capacity was determined ex vivo after exposure of murine macrophages to apolipoprotein B-depleted patient sera obtained at baseline and after 12 weeks. After 12 weeks, HIV RNA decreased most in subjects randomized to ART. Available data on cholesterol demonstrated that efflux capacity from Abca1+/+ macrophages was increased most by sera obtained from ART-treated subjects (20.5% ± 5.0% to 24.3 % ± 6.9%, baseline to 12 weeks, P = .007; ART group [n = 6] vs 18.0 % ± 3.9% to 19.1 % ± 2.9%, baseline to 12 weeks, P = .30; untreated group [n = 6] [P = .04 ART vs untreated group]). Change in HIV RNA was negatively associated with change in Abca1+/+ macrophage cholesterol efflux (r = − 0.62, P = .03), and this finding remained significant (P = .03) after controlling for changes in HDL-cholesterol, CD4+ cells, and markers of monocyte or macrophage activation. In subjects acutely infected with HIV, ATP-binding cassette transporter A1-mediated cholesterol efflux was stimulated to a greater degree over time by apolipoprotein B-depleted serum from subjects randomized to ART. The improvement in cholesterol efflux capacity is independently related to reduction in viral load.