Immune activation, immunosenescence, and osteoprotegerin as markers of endothelial dysfunction in subclinical HIV-associated atherosclerosis

Mediators Inflamm. 2014:2014:192594. doi: 10.1155/2014/192594. Epub 2014 Oct 14.

Abstract

HIV-infected patients have a significantly greater risk of cardiovascular disease. Several markers including osteoprotegerin have been shown to be involved in the development and progression of atherosclerosis. We investigated the relationship between T-cell phenotype, osteoprotegerin, and atherosclerosis evaluated by carotid intima-media thickness (c-IMT) in 94 HIV+ patients on suppressive antiretroviral therapy with Framingham score <10%. As for the control group, 24 HIV-negative subjects were enrolled. c-IMT was assessed by ultrasound. CD4+/CD8+ T-cell activation (CD38+ HLADR+) and senescence (CD57+ CD28-) were measured by flow cytometry. IL-6 and OPG levels were measured by ELISA kit. c-IMT was higher in HIV+ than in controls. Among HIV+ patients, 44.7% had pathological c-IMT (≥0.9 mm). CD8+ T-cell activation and senescence and OPG plasma levels were higher in HIV+ patients than in controls. Subjects with pathological c-IMT exhibited higher CD8+ immune activation and immunosenescence and OPG levels than subjects with normal c-IMT. Multivariate analysis showed that age, CD8+ CD38+ HLADR+, and CD8+ CD28- CD57+ were independently associated with pathological c-IMT. Several factors have been implicated in the pathogenesis of atherosclerosis in HIV patients. Immune activation and immunosenescence of CD8+ T cell together with OPG plasma levels might be associated with the development and progression of early atherosclerosis, even in the case of viral suppression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use
  • Atherosclerosis / etiology*
  • Atherosclerosis / immunology*
  • Biomarkers / blood
  • CD8-Positive T-Lymphocytes / immunology
  • Carotid Intima-Media Thickness
  • Case-Control Studies
  • Cellular Senescence / immunology
  • Disease Progression
  • Female
  • HIV Infections / complications*
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • Humans
  • Interleukin-6 / blood
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Osteoprotegerin / blood*

Substances

  • Anti-HIV Agents
  • Biomarkers
  • IL6 protein, human
  • Interleukin-6
  • Osteoprotegerin
  • TNFRSF11B protein, human