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AIDS. 2015 Jul 31;29(12):1445-57. doi: 10.1097/QAD.0000000000000739.

Monocytes from HIV-infected individuals show impaired cholesterol efflux and increased foam cell formation after transendothelial migration.

Author information

1
aCentre for Biomedical Research, Burnet Institute bDepartment of Infectious Diseases, Monash University cSchool of Applied Sciences, RMIT University dMonash Micro Imaging, Monash University eDepartment of Microbiology and Immunology, Melbourne University, Melbourne, Victoria, Australia fFeinberg School of Medicine, Northwestern University, Chicago, Illinois, USA gDepartment of Immunology, Monash University, Melbourne, Victoria, Australia.

Abstract

DESIGN:

HIV-infected (HIV+) individuals have an increased risk of atherosclerosis and cardiovascular disease which is independent of antiretroviral therapy and traditional risk factors. Monocytes play a central role in the development of atherosclerosis, and HIV-related chronic inflammation and monocyte activation may contribute to increased atherosclerosis, but the mechanisms are unknown.

METHODS:

Using an in-vitro model of atherosclerotic plaque formation, we measured the transendothelial migration of purified monocytes from age-matched HIV+ and uninfected donors and examined their differentiation into foam cells. Cholesterol efflux and the expression of cholesterol metabolism genes were also assessed.

RESULTS:

Monocytes from HIV+ individuals showed increased foam cell formation compared with controls (18.9 vs. 0%, respectively, P = 0.004) and serum from virologically suppressed HIV+ individuals potentiated foam cell formation by monocytes from both uninfected and HIV+ donors. Plasma tumour necrosis factor (TNF) levels were increased in HIV+ vs. control donors (5.9 vs. 3.5 pg/ml, P = 0.02) and foam cell formation was inhibited by blocking antibodies to TNF receptors, suggesting a direct effect on monocyte differentiation to foam cells. Monocytes from virologically suppressed HIV+ donors showed impaired cholesterol efflux and decreased expression of key genes regulating cholesterol metabolism, including the cholesterol transporter ABCA1 (P = 0.02).

CONCLUSION:

Monocytes from HIV+ individuals show impaired cholesterol efflux and are primed for foam cell formation following transendothelial migration. Factors present in HIV+ serum, including elevated TNF levels, further enhance foam cell formation. The proatherogenic phenotype of monocytes persists in virologically suppressed HIV+ individuals and may contribute mechanistically to increased atherosclerosis in this population.

PMID:
26244384
PMCID:
PMC5086669
DOI:
10.1097/QAD.0000000000000739
[Indexed for MEDLINE]
Free PMC Article

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