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

Maisa A, Hearps AC, Angelovich TA, Pereira CF, Zhou J, Shi MDY, Palmer CS, Muller WA, Crowe SM, Jaworowski A


Design: HIV-infected (HIVþ) 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 HIVþ 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 HIVþ individuals showed increased foam cell formation compared with controls (18.9 vs. 0%, respectively, P¼0.004) and serum from virologically suppressed HIVþ individuals potentiated foam cell formation by monocytes from both uninfected and HIVþ donors. Plasma tumour necrosis factor (TNF) levels were increased in HIVþ vs. control donors (5.9 vs. 3.5 pg/ml, P¼0.02) 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 HIVþ donors showed impaired cholesterol efflux and decreased expression of key genes regulating cholesterol metabolism, including the cholesterol transporter ABCA1 (P¼0.02). Conclusion: Monocytes from HIVþ individuals show impaired cholesterol efflux and are primed for foam cell formation following transendothelial migration. Factors present in HIVþ serum, including elevated TNF levels, further enhance foam cell formation. The proatherogenic phenotype of monocytes persists in virologically suppressed HIVþ individuals and may contribute mechanistically to increased atherosclerosis in this population.


  • Journal: AIDS
  • Published: 15/06/2015
  • Volume: 29
  • Issue: 12
  • Pagination: 1445-1457


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