Monocytes from men living with HIV exhibit heightened atherogenic potential despite long-term viral suppression with antiretroviral therapy

被引:10
作者
Angelovich, Thomas A. [1 ,2 ]
Trevillyan, Janine M. [3 ,4 ]
Hoy, Jennifer F. [3 ,4 ]
Wong, Michelle E. [1 ,5 ]
Agius, Paul A. [1 ,6 ]
Hearps, Anna C. [1 ,3 ,4 ]
Jaworowski, Anthony [1 ,2 ,3 ,4 ]
机构
[1] Burnet Inst, Hlth Ageing Program, GPO Box 2284, Melbourne, Vic 3001, Australia
[2] RMIT Univ, Sch Hlth & Biomed Sci, Chron Infect & Inflammatory Dis Res, Melbourne, Vic, Australia
[3] Alfred Hosp, Dept Infect Dis, Melbourne, Vic, Australia
[4] Monash Univ, Melbourne, Vic, Australia
[5] Monash Univ, Cent Clin Sch, Melbourne, Vic, Australia
[6] Monash Univ, Sch Publ Hlth & Prevent Med, Melbourne, Vic, Australia
基金
英国医学研究理事会;
关键词
atherosclerosis; foam cell; HIV; monocyte; oxidized HDL; FOAM CELL-FORMATION; HIGH-DENSITY-LIPOPROTEIN; ARTERIAL INFLAMMATION; INDIVIDUALS; ATHEROSCLEROSIS; PROGRESSION; METABOLISM; MARKERS;
D O I
10.1097/QAD.0000000000002460
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Objective: 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. Methods: 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. Results: 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). Conclusion: 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.
引用
收藏
页码:513 / 518
页数:6
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