Abstract 16803: Subclinical Atherosclerosis is Associated With Loss Of CXCR4 Surface Marker Expression on Non-classical Monocytes in HIV-infected Women
Introduction: HIV infection is associated with increased risk of cardiovascular disease (CVD). Identification of immunologic mechanisms associated with subclinical CVD (sCVD) among HIV-positive individuals may improve CVD risk assessment and preventive strategies. CXCR4 is a co-receptor for HIV entry and a chemokine receptor for CXCL12 and macrophage migration inhibitory factor. CXCR4 expression has been associated with susceptibility of monocytes to HIV infection and atherosclerosis.
Hypothesis: HIV infection and sCVD are associated with CXCR4 expression on classical (CD14++), intermediate (CD14+CD16+), and non-classical (CD14dimCD16+) monocytes in women.
Methods: The three subsets of monocytes were counted and phenotyped for the surface markers CD14, CD16, and CXCR4 by flow cytometry. sCVD was assessed by high-resolution carotid ultrasound in 92 participants of the Women’s Interagency HIV Study (WIHS) and defined as one or more atherosclerotic lesions (focal IMT >1.5 mm) in the carotid artery. Participants were stratified into 4 sets (n=23 each) by HIV and sCVD status (HIV-/sCVD-, HIV-/sCVD+, HIV+/sCVD-, HIV+/sCVD+) and matched by age, race/ethnicity, and smoking status.
Results: Median age was 51.5 years (IQR 47-58). We found no changes in monocyte subset sizes among the 4 groups. CXCR4 expression (median fluorscence intensity, MFI) in non-classical monocytes was highest among HIV-/CVD- women (MFI 917±880), followed by HIV-/CVD+ (505±439), HIV+/CVD- (481±277), and lowest in HIV+/CVD+ women (360±433), overall P=0.006. In regression analyses of matched samples that were adjusted for education, study site, and history of injection drug use, presence of HIV infection and sCVD remained significantly associated with lower CXCR4 expression on non-classical monocytes (Table).
Conclusion: CXCR4 expression in non-classical monocytes is reduced among women with both HIV infection and sCVD suggesting an important role of CXCR4 signaling in atherogenesis.
Author Disclosures: K.A. Mueller: None. D.B. Hanna: None. E. Ehinger: None. X. Xue: None. L. Baas: None. K. Anastos: None. M.H. Cohen: None. S.J. Gange: None. S.L. Heath: None. J.M. Lazar: None. C. Liu: None. W.J. Mack: None. I. Ofotokun: None. P.C. Tien: None. H.N. Hodis: None. A.L. Landay: None. R.C. Kaplan: None. R.C. Kaplan: None. K. Ley: None.
- © 2016 by American Heart Association, Inc.