Healthy Ageing Program, Burnet Institute.
Chronic Infectious and Inflammatory Diseases Research, School of Health and Biomedical Sciences, RMIT University.
AIDS. 2020 Mar 15;34(4):513-518. doi: 10.1097/QAD.0000000000002460.
People living with HIV have an increased risk of cardiovascular disease (CVD) despite effective antiretroviral therapy (ART). Monocytes play a key role in the early stages of atherosclerosis-driven CVD by forming lipid-laden foam cells within artery walls. HIV infection potentiates foam cell formation ex vivo, but the mechanisms contributing to this are not known.
We investigated the atherosclerosis-promoting potential of monocytes from 39 virologically suppressed men living with HIV (MLHIV) on ART and no evidence of CVD, and 25 HIV-uninfected controls of comparable age, sex, smoking status and CVD risk.
Despite absence of clinical atherosclerosis in both MLHIV and uninfected cohorts (evidenced by a carotid intima-media thickness of 0.6 mm for both groups; P = 0.254), monocytes from MLHIV showed increased potential to form atherosclerosis-promoting foam cells compared with controls in an ex-vivo assay (36.6% vs. 27.6%, respectively, P = 0.003). Consistent with observations of persistent inflammation and immune/endothelial activation in ART-treated HIV infection, levels of soluble tumour necrosis factor receptor II, CXCL10 and soluble VCAM-1 were elevated in MLHIV (P ≤ 0.005 for all), but were not significantly associated with foam cell formation. Foam cell formation was associated with an impaired ability of monocytes to undergo reverse transmigration, and a reduced ability to efflux cholesterol ex vivo (P < 0.05 for both). Importantly, foam cell formation declined significantly with duration of viral suppression (P = 0.004).
These findings highlight the persistence of HIV-related changes to the atherogenic potential of monocytes despite long-term viral suppression, and provide insights into mechanisms potentially driving increased CVD in ART-treated HIV infection.
尽管有有效的抗逆转录病毒疗法（ART），但 HIV 感染者患心血管疾病（CVD）的风险仍然增加。单核细胞通过在动脉壁内形成富含脂质的泡沫细胞，在动脉粥样硬化驱动的 CVD 的早期阶段发挥关键作用。HIV 感染增强了体外泡沫细胞的形成，但导致这种情况的机制尚不清楚。
我们研究了 39 名接受 ART 治疗且无 CVD 证据的 HIV 感染者（MLHIV）和 25 名年龄、性别、吸烟状况和 CVD 风险相当的未感染 HIV 的对照者的单核细胞的动脉粥样硬化促进潜力。
尽管 MLHIV 和未感染组均无临床动脉粥样硬化（两组颈动脉内膜中层厚度均为 0.6mm；P=0.254），但在体外实验中，MLHIV 的单核细胞形成促进动脉粥样硬化的泡沫细胞的潜力比对照组高（分别为 36.6%和 27.6%，P=0.003）。与接受 ART 治疗的 HIV 感染中持续炎症和免疫/内皮激活的观察结果一致，可溶性肿瘤坏死因子受体 II、CXCL10 和可溶性 VCAM-1 水平在 MLHIV 中升高（均 P≤0.005），但与泡沫细胞形成无显著相关性。泡沫细胞形成与单核细胞反向迁移能力受损和体外胆固醇外排能力降低有关（均 P<0.05）。重要的是，泡沫细胞形成随着病毒抑制时间的延长而显著下降（P=0.004）。
这些发现强调了尽管长期病毒抑制，但 HIV 相关变化对单核细胞致动脉粥样硬化潜力的持续存在，并提供了对潜在机制的深入了解，这些机制可能导致接受 ART 治疗的 HIV 感染中 CVD 增加。
