Endothelial dysfunction, arterial stiffening, and intima-media thickening in large arteries from HIV-1 transgenic mice.
Endothelial dysfunction, arterial stiffening, and intima-media thickening in large arteries from HIV-1 transgenic mice.
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DOI：
10.1007/s10439-012-0702-5
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发表时间：
2013-04
影响因子：
3.8
通讯作者：
Gleason, Rudolph L., Jr.
中科院分区：
文献类型：
--
作者：
Hansen, Laura;Parker, Ivana;Sutliff, Roy L.;Platt, Manu O.;Gleason, Rudolph L., Jr.
接受高效抗逆转录病毒治疗（HAART）的HIV患者表现出心血管疾病的发病率升高，包括心肌梗死的风险和动脉粥样硬化病变的患病率较高，以及亚临床动脉粥样硬化的标志物增加，包括颈动脉内膜中层厚度增加，动脉僵硬度增加和血流介导的扩张受损。HAART和HIV感染是动脉粥样硬化和心肌梗死的独立危险因素。研究表明HIV蛋白达特、gp 120、vpu和nef与早期动脉粥样硬化有关。本研究的目的是量化HIV-1蛋白表达对颈总动脉和颈动脉的血管功能、生物力学和几何形状的作用。本研究使用了NL 4 -3Δ gag/pol转基因小鼠（HIV-Tg），其含有HIV-1蛋白env、达特、nef、rev、vif、vpr和vpu的遗传序列，但缺乏gag和pol基因，并报告HIV-Tg小鼠主动脉内皮功能受损、颈动脉内膜中层厚度（c-IMT）增加和动脉僵硬度增加。此外，HIV-Tg动脉显示弹性蛋白含量降低，组织蛋白酶K和组织蛋白酶S活性增加，以及机械残余应力增加。因此，表达HIV蛋白的小鼠表现出动脉粥样硬化的临床前标志物，并且这些标志物与血管重塑标志物的变化相关。这些发现与HIV蛋白质独立于HAART治疗或HIV感染可能在心血管疾病的发展中发挥作用的假设一致。
HIV patients on highly active antiretroviral therapy (HAART) exhibit elevated incidence of cardiovascular disease, including a higher risk of myocardial infarction and prevalence of atherosclerotic lesions, as well as increases in markers of subclinical atherosclerosis including increased carotid artery intima-media thickness, increased arterial stiffness, and impaired flow-mediated dilation. Both HAART and HIV-infection are independent risk factors for atherosclerosis and myocardial infarction. Studies implicate the HIV proteins tat, gp120, vpu, and nef in early on-set atherosclerosis. The objective of this study was to quantify the role of expression of HIV-1 proteins on the vascular function, biomechanics, and geometry of common carotid arteries and aortas. This study employed NL4-3Δ gag/pol transgenic mice (HIV-Tg), which contain the genetic sequence for the HIV-1 proteins env, tat, nef, rev, vif, vpr, and vpu but lacks the gag and pol genes and reports that HIV-Tg mice have impaired aortic endothelial function, increased carotid intima-media thickness (c-IMT), and increased arterial stiffness. Further, HIV-Tg arteries show decreased elastin content, increased cathepsin K and cathepsin S activity, and increased mechanical residual stress. Thus, mice that express HIV proteins exhibit pre-clinical markers of atherosclerosis and these markers correlate with changes in markers of vascular remodeling. These findings are consistent with the hypothesis that HIV-proteins, independent of HAART treatment or HIV infection, could play a role in of the development of cardiovascular disease.
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影响因子：
3.8
作者：
Mary-Krause, M;Cotteb, L;Costagliola, D
通讯作者：
Costagliola, D
影响因子：
37.8
作者：
Lutgens, E;Lutgens, SPM;Cleutjens, KBJM
通讯作者：
Cleutjens, KBJM
影响因子：
6.4
作者：
Grubb, JR;Dejam, A;Gladwin, MT
通讯作者：
Gladwin, MT
影响因子：
37.8
作者：
Hsue, PY;Lo, JC;Waters, DD
通讯作者：
Waters, DD
DOI：
10.1097/qad.0b013e32830fe35e
发表时间：
2008-09-12
期刊：
AIDS (London, England)
影响因子：
--
作者：
Strategies for Management of Anti-Retroviral Therapy/INSIGHT;DAD Study Groups
通讯作者：
DAD Study Groups