Reduced CD14 expression on classical monocytes and vascular endothelial adhesion markers independently associate with carotid artery intima media thickness in chronically HIV-1 infected adults on virologically suppressive anti-retroviral therapy

Atherosclerosis. 2014 Jan;232(1):52-8. doi: 10.1016/j.atherosclerosis.2013.10.021. Epub 2013 Oct 31.

Abstract

HIV infection causes systemic immune inflammation, and increases the risk for cardiovascular (CVD) disease even among those on virologically suppressive anti-retroviral treatment (ART). We performed a biostatistical analysis and screen of candidate cellular and plasma biomarkers for association with carotid artery intima-media thickness (CIMT), independent of traditional CVD risk factors such as age, gender, systolic blood pressure (SBP), lipid levels, smoking and diabetes. We conducted a multi-stage analysis based on a cross-sectional study of CVD risk in HIV-infected subjects age >45 years on ART for >6 months. The goal of this analysis was to identify candidate cellular and plasma biomarkers of CIMT in HIV-1 infected adults. We further sought to determine if these candidate biomarkers were independent of traditional CVD risk factors previously identified in HIV negative adults. High-resolution B-mode ultrasound images of the right common carotid common artery (CCA) were obtained. Plasma soluble inflammatory mediators, cytokines and chemokines were detected. Monocytes were defined by CD14/CD16 expression, and CD8+ T-cell activation by CD38/HLA-DR expression. Subjects were a median of 49.5 years old, 87% male, had a CIMT of 0.73 mm, FRS of 6%, a median viral load of 48 copies/mL, and CD4+ T cell count of 479 cells/μL. Soluble VCAM-1, and expansion of CD14dimCD16- monocytes each associated with higher CIMT independently of age and SBP. These factors are distinct components of a shared atherogenic process; 1) vascular endothelial molecular expression and 2) vascular monocytes that enter into the vascular endothelium and promote atherosclerotic plaque.

Keywords: Biomarker; CD14; CIMT; Cardiovascular disease; Carotid intima-media; Cytokines; Framingham risk score; HIV; Monocytes; Regression; Screen; VCAM-1.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Biomarkers / metabolism
  • Blood Pressure
  • Cardiovascular Diseases / metabolism*
  • Carotid Arteries / pathology*
  • Carotid Intima-Media Thickness*
  • Cohort Studies
  • Cross-Sectional Studies
  • Cytokines / metabolism
  • Endothelial Cells / cytology*
  • Female
  • GPI-Linked Proteins / metabolism
  • HIV Infections / complications*
  • HIV Infections / drug therapy
  • Humans
  • Lipopolysaccharide Receptors / metabolism*
  • Male
  • Middle Aged
  • Monocytes / cytology
  • Monocytes / metabolism*
  • Phenotype
  • Receptors, IgG / metabolism
  • Risk Factors
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Biomarkers
  • Cytokines
  • FCGR3B protein, human
  • GPI-Linked Proteins
  • Lipopolysaccharide Receptors
  • Receptors, IgG
  • Vascular Cell Adhesion Molecule-1