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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Atherosclerosis / pathology*
  • Biological Transport
  • Cell Differentiation*
  • Cells, Cultured
  • Cholesterol / metabolism*
  • Foam Cells / metabolism
  • Foam Cells / physiology*
  • HIV Infections / complications
  • HIV Infections / pathology*
  • Humans
  • Male
  • Middle Aged
  • Models, Theoretical
  • Monocytes / metabolism
  • Monocytes / physiology*
  • Transendothelial and Transepithelial Migration*

Substances

  • Cholesterol