Chronic Exposure to HIV-Derived Protein Tat Impairs Endothelial Function via Indirect Alteration in Fat Mass and Nox1-Mediated Mechanisms in Mice.
Chronic Exposure to HIV-Derived Protein Tat Impairs Endothelial Function via Indirect Alteration in Fat Mass and Nox1-Mediated Mechanisms in Mice.
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慢性暴露于hiv衍生蛋白Tat通过间接改变小鼠脂肪量和nox1介导的机制损害内皮功能。
DOI：
10.3390/ijms222010977
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发表时间：
2021-10-12
影响因子：
5.6
通讯作者：
Belin de Chantemèle EJ
中科院分区：
文献类型：
--
作者：
Kovacs L;Bruder-Nascimento T;Greene L;Kennard S;Belin de Chantemèle EJ
携带人类免疫缺陷病毒(PLWH)的人患动脉粥样硬化相关心血管疾病(CVD)的风险增加，CVD是这一人群的主要死亡原因。尽管如此，HIV相关血管发病机制仍未完全阐明。因此，我们试图确定HIV调节蛋白TAT是否通过NADPH氧化酶1(Nox1)依赖的机制来介导HIV诱导的内皮功能障碍。观察TAT对C57BL/6雄性小鼠的体重、脂肪质量、瘦素水平、ROS产生酶的表达及血管功能的影响。在体外和体外环境下，用TAT处理主动脉环和人内皮细胞2-24小时。慢性(4周)而非急性(3天和2-24小时)的TAT治疗降低了体重、脂肪质量和瘦素水平，并增加了Nox1及其辅活化子NADPH氧化酶激活剂1(NoxA1)的表达。这与内皮依赖性血管松弛受损有关。重要的是，用GKT771特异性抑制Nox1和长期注射瘦素可以恢复TAT处理的小鼠的内皮功能。这些数据排除了HIV-TAT对内皮功能的直接影响，并暗示脂肪质量和瘦素产生的减少可能解释了Nox1和NoxA1表达上调的原因。Nox1和Leptin系统可能为改善HIV感染相关心血管疾病的血管功能提供潜在的靶点。
People living with human immunodeficiency virus (HIV) (PLWH) have increased risk for atherosclerosis-related cardiovascular disease (CVD), the main cause of death in this population. Notwithstanding, the mechanisms of HIV-associated vascular pathogenesis are not fully elucidated. Therefore, we sought to determine whether HIV-regulatory protein Tat mediates HIV-induced endothelial dysfunction via NADPH oxidase 1 (Nox1)-dependent mechanisms. Body weight, fat mass, leptin levels, expression of reactive oxygen species (ROS)-producing enzymes and vascular function were assessed in C57BL/6 male mice treated with Tat for 3 days and 4 weeks. Aortic rings and human endothelial cells were also treated with Tat for 2–24 h in ex vivo and in vitro settings. Chronic (4 weeks) but not acute (3 days and 2–24 h) treatment with Tat decreased body weight, fat mass, and leptin levels and increased the expression of Nox1 and its coactivator NADPH oxidase Activator 1 (NoxA1). This was associated with impaired endothelium-dependent vasorelaxation. Importantly, specific inhibition of Nox1 with GKT771 and chronic leptin infusion restored endothelial function in Tat-treated mice. These data rule out direct effects of HIV-Tat on endothelial function and imply the contribution of reductions in adipose mass and leptin production which likely explain upregulated expression of Nox1 and NoxA1. The Nox1 and leptin system may provide potential targets to improve vascular function in HIV infection-associated CVD.
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影响因子：
11.4
作者：
El-Amine R;Germini D;Zakharova VV;Tsfasman T;Sheval EV;Louzada RAN;Dupuy C;Bilhou-Nabera C;Hamade A;Najjar F;Oksenhendler E;Lipinski M;Chernyak BV;Vassetzky YS
通讯作者：
Vassetzky YS
影响因子：
5.4
作者：
Alonso, Alvaro;Barnes, A. Elise;Marconi, Vincent
通讯作者：
Marconi, Vincent
影响因子：
6.4
作者：
Freeman, LM;Mansfield, KG;Gorbach, SL
通讯作者：
Gorbach, SL
影响因子：
37.8
作者：
Huby, Anne-Cecile;Antonova, Galina;de Chantemele, Eric J. Belin
通讯作者：
de Chantemele, Eric J. Belin
DOI：
10.1073/pnas.90.16.7632
发表时间：
1993-08-15
影响因子：
11.1
作者：
FLORES, SC;MARECKI, JC;MCCORD, JM
通讯作者：
MCCORD, JM