Circulating Microparticles Are Elevated in Treated HIV-1 Infection and Are Deleterious to Endothelial Cell Function
Circulating Microparticles Are Elevated in Treated HIV-1 Infection and Are Deleterious to Endothelial Cell Function
复制标题
DOI：
10.1161/jaha.118.011134
复制
发表时间：
2019-02-19
影响因子：
5.4
通讯作者：
DeSouza, Christopher A.
中科院分区：
文献类型：
--
作者：
Hijmans, Jamie G.;Stockelman, Kelly A.;DeSouza, Christopher A.
循环微粒已成为血管疾病的生物标志物和效应物。心血管疾病的发病率在HIV-1血清反应阳性的个体中有所升高。本研究的目的是确定：（1）在接受抗逆转录病毒治疗的HIV-1血清阳性成人中，循环微粒是否升高;和（2）从抗逆转录病毒治疗的HIV-1血清阳性成人中分离的微粒对内皮细胞功能的体外作用。方法和结果-内皮细胞、血小板、单核细胞的循环水平，通过流式细胞术测定15名健康和15名经抗逆转录病毒治疗、病毒学抑制的HIV-1血清阳性男性的血浆中白细胞衍生的微粒。用来自个体受试者的微粒处理人脐静脉内皮细胞24小时;此后，评估内皮细胞炎症、氧化应激、衰老和凋亡。与健康男性相比，HIV-1血清阳性者的内皮细胞、血小板、单核细胞和白细胞衍生微粒的循环浓度显著较高（约为35%-225%）。来自HIV-1血清阳性男性的微粒诱导显著更大的内皮细胞释放白细胞介素-6和白细胞介素-8（分别约为20%和35%）和核因子jB表达，同时抑制抗炎microRNA（miR-146 a和miR-181 b）。细胞内活性氧的产生和活性氧相关的热休克蛋白70的表达都较高的细胞与微粒处理的HIV-1血清阳性男子。此外，在用HIV-1相关微粒处理的细胞中，衰老细胞的百分比显著更高，sirtuin 1表达更低。最后，胱天蛋白酶-3显着升高微粒从HIV-1血清阳性的man. Conclusions循环浓度的内皮细胞，血小板，单核细胞和白细胞衍生的微粒较高的抗逆转录病毒治疗HIV-1血清阳性的男子和不利影响内皮细胞促进细胞炎症，氧化应激，衰老和凋亡。循环微粒可能有助于与HIV-1感染相关的血管风险。
Background-Circulating microparticles have emerged as biomarkers and effectors of vascular disease. Elevated rates of cardiovascular disease are seen in HIV-1-seropositive individuals. The aims of this study were to determine: (1) if circulating microparticles are elevated in antiretroviral therapy-treated HIV-1-seropositive adults; and (2) the effects of microparticles isolated from antiretroviral therapy-treated HIV-1-seropositive adults on endothelial cell function, in vitro.Methods and Results-Circulating levels of endothelial-, platelet-, monocyte-, and leukocyte-derived microparticles were determined by flow cytometry in plasma from 15 healthy and 15 antiretroviral therapy-treated, virologically suppressed HIV-1-seropositive men. Human umbilical vein endothelial cells were treated with microparticles from individual subjects for 24 hours; thereafter, endothelial cell inflammation, oxidative stress, senescence, and apoptosis were assessed. Circulating concentrations of endothelial-, platelet-, monocyte-, and leukocyte-derived microparticles were significantly higher (approximate to 35%-225%) in the HIV-1-seropositive compared with healthy men. Microparticles from HIV-1-seropositive men induced significantly greater endothelial cell release of interleukin-6 and interleukin-8 (approximate to 20% and approximate to 35%, respectively) and nuclear factor-jB expression while suppressing anti-inflammatory microRNAs (miR-146a and miR-181b). Intracellular reactive oxygen species production and expression of reactive oxygen species-related heat shock protein 70 were both higher in cells treated with microparticles from the HIV-1-seropositive men. In addition, the percentage of senescent cells was significantly higher and sirtuin 1 expression lower in cells treated with HIV-1-related microparticles. Finally, caspase-3 was significantly elevated by microparticles from HIV-1-seropositive men.Conclusions-Circulating concentrations of endothelial-, platelet-, monocyte-, and leukocyte-derived microparticles were higher in antiretroviral therapy-treated HIV-1-seropositive men and adversely affect endothelial cells promoting cellular inflammation, oxidative stress, senescence, and apoptosis. Circulating microparticles may contribute to the vascular risk associated with HIV-1 infection.