Abstract

OBJECTIVE: The role of HDL function in HIV-related atherosclerotic cardiovascular disease (CVD) is unclear. HDLs isolated from HIV+ [HIV(+)HDL] and HIV-uninfected individuals (HDL) were assessed for HDL function and ability to promote monocyte-derived foam cell formation (MDFCF) (a key event in HIV-related CVD) ex vivo.

DESIGN/METHODS: Using an established in vitro model of atherogenesis and plasma samples from an established cross-sectional study of virologically-suppressed HIV+ males on stable effective antiretroviral therapy (ART) and with low CVD risk (median age: 42 years; n = 10), we explored the impact of native HDL [HIV(+)HDL] on MDFCF. In this exploratory study we selected HIV-HDL known to be dysfunctional based on two independent measures of impaired HDL function: a) antioxidant (high HDLox) b) ability of HDL to release apoA-I [low HDL-apoA-I exchange (HAE %)]. Five healthy males matched by age and race to the HIV+ group were included. Given that oxidation of HDL leads to abnormal HDL function, we also compared proatherogenic effects of HIV-HDL versus chemically-derived HDLox. The ex vivo atherogenesis assay was performed using lipoproteins (purchased or isolated from plasma using ultracentrifugation) and monocytes purified via negative selection from healthy donors.

RESULTS: HIV(+)HDL known to have reduced antioxidant function and rate of HDL/ApoAI exchange promoted MDFCF to a greater extent than HDL (33.0% vs 26.2% foam cells; p = 0.015). HDL oxidized in vitro also enhanced foam cell formation as compared to non-oxidized HDL (p < 0.01).

CONCLUSION: Dysfunctional HDL in virologically suppressed HIV+ individuals may potentiate atherosclerosis in HIV infection by promoting monocyte-derived foam cell formation.The role of HDL function in HIV-related atherosclerotic cardiovascular disease is unclear. HDL isolated from HIV+ [HIV(+)HDL] and HIV-uninfected individuals [HIV(-)HDL] were assessed for HDL function and ability to promote foam cell formation ex vivo. HIV(+)HDL known to have reduced antioxidant function and rate of HDL/ApoA1 exchange promoted monocyte-derived foam cell formation to a greater extent than HDL(-)HDL (33.0% vs 26.2% foam cells; p = 0.015). HDL oxidized in vitro also enhanced foam cell formation as compared with non-oxidized HDL (p = 0.01). Dysfunctional HDL in virologically suppressed HIV+ individuals may potentiate atherosclerosis in HIV infection by promoting monocyte-derived foam cell formation.

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