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

Anna Maisa, Anna C. Hearps, Thomas A. Angelovich, Candida F. Pereira, Jingling Zhou, Margaret D.Y. Shi, Clovis S. Palmer, William A. Muller, Suzanne M. Crowe, Anthony Jaworowski*

*Corresponding author for this work

Research output: Contribution to journalArticle

28 Scopus citations

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, P0.004) 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, P0.02) 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 (P0.02). 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 HIVP individuals and may contribute mechanistically to increased atherosclerosis in thispopulation.

Original languageEnglish (US)
Pages (from-to)1445-1457
Number of pages13
JournalAIDS
Volume29
Issue number12
DOIs
StatePublished - Jul 31 2015

Keywords

  • Atherosclerosis
  • Cholesterol efflux
  • Foam cells
  • HIV
  • Innate immune activation
  • Macrophage
  • Monocytes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Monocytes from HIV-infected individuals show impaired cholesterol efflux and increased foam cell formation after transendothelial migration'. Together they form a unique fingerprint.

  • Cite this

    Maisa, A., Hearps, A. C., Angelovich, T. A., Pereira, C. F., Zhou, J., Shi, M. D. Y., Palmer, C. S., Muller, W. A., Crowe, S. M., & Jaworowski, A. (2015). Monocytes from HIV-infected individuals show impaired cholesterol efflux and increased foam cell formation after transendothelial migration. AIDS, 29(12), 1445-1457. https://doi.org/10.1097/QAD.0000000000000739