PDF(Pubmed)
Abstract：
Persistent immune activation is linked to an increased risk of cardiovascular disease (CVD) in people with HIV (PWH) on antiretroviral therapy (ART). The NLRP3 inflammasome may contribute to elevated CVD risk in PWH. This study utilized peripheral blood mononuclear cells (PBMCs) from 25 PWH and 25 HIV-negative controls, as well as HIV in vitro infections. Transcriptional changes were analyzed using RNAseq and pathway analysis. Our results showed that in vitro HIV infection of macrophages and PBMCs from PWH had increased foam cell formation and expression of the NLRP3 inflammasome components and downstream cytokines (caspase-1, IL-1β, and IL-18), which was reduced with inhibition of NLRP3 activity using MCC950. Transcriptomic analysis revealed an increased expression of multiple genes involved in lipid metabolism, cholesterol storage, coronary microcirculation disorders, ischemic events, and monocyte/macrophage differentiation and function with HIV infection and oxLDL treatment. HIV infection and NLRP3 activation increased foam cell formation and expression of proinflammatory cytokines, providing insights into the mechanisms underlying HIV-associated atherogenesis. This study suggests that HIV itself may contribute to increased CVD risk in PWH. Understanding the involvement of the inflammasome pathway in HIV atherosclerosis can help identify potential therapeutic targets to mitigate cardiovascular risks in PWH.
摘要：
持续的免疫激活与抗逆转录病毒治疗（ART）的HIV感染者（PWH）患心血管疾病（CVD）的风险增加有关。NLRP3炎性体可能导致PWH中CVD风险升高。这项研究利用了来自25个PWH和25个HIV阴性对照的外周血单核细胞（PBMC），以及艾滋病毒的体外感染。使用RNAseq和通路分析分析转录变化。我们的结果表明，来自PWH的巨噬细胞和PBMC的体外HIV感染增加了泡沫细胞的形成和NLRP3炎性体成分和下游细胞因子的表达（caspase-1，IL-1β，和IL-18），其随着使用MCC950抑制NLRP3活性而降低。转录组学分析显示，参与脂质代谢的多个基因表达增加，胆固醇储存，冠状动脉微循环障碍，缺血事件，和单核细胞/巨噬细胞分化和功能与HIV感染和oxLDL治疗。HIV感染和NLRP3激活增加泡沫细胞形成和促炎细胞因子的表达，提供对HIV相关动脉粥样硬化形成的潜在机制的见解。这项研究表明，艾滋病毒本身可能导致PWH中CVD风险增加。了解炎症小体途径在HIV动脉粥样硬化中的参与可以帮助确定潜在的治疗靶标，以减轻PWH中的心血管风险。
