1. Loss of CXCR4 on non-classical monocytes in participants of the Women’s Interagency HIV Study (WIHS) with subclinical atherosclerosis
- Author
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Phyllis C. Tien, Meinrad Gawaz, Robert C. Kaplan, Wendy J. Mack, Alan L. Landay, Jason Lazar, Xiaonan Xue, Howard N. Hodis, Stephen J. Gange, Erik Ehinger, Igho Ofotokun, Tobias Geisler, Kathryn Anastos, Mardge H. Cohen, David B. Hanna, Karin Mueller, Sonya L. Heath, Chenglong Liu, Klaus Ley, and Livia Baas
- Subjects
Adult ,Carotid Artery Diseases ,0301 basic medicine ,Receptors, CXCR4 ,medicine.medical_specialty ,Physiology ,Human immunodeficiency virus (HIV) ,Down-Regulation ,HIV Infections ,030204 cardiovascular system & hematology ,medicine.disease_cause ,Peripheral blood mononuclear cell ,Gastroenterology ,CXCR4 ,Monocytes ,03 medical and health sciences ,Sex Factors ,0302 clinical medicine ,Interquartile range ,Antiretroviral Therapy, Highly Active ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,cardiovascular diseases ,Subclinical infection ,business.industry ,Monocyte ,virus diseases ,Original Articles ,Women's Interagency HIV Study ,Middle Aged ,Plaque, Atherosclerotic ,Cross-Sectional Studies ,Phenotype ,030104 developmental biology ,medicine.anatomical_structure ,Blood pressure ,Asymptomatic Diseases ,Female ,Cardiology and Cardiovascular Medicine ,business ,Biomarkers - Abstract
AimsTo test whether human immunodeficiency virus (HIV) infection and subclinical cardiovascular disease (sCVD) are associated with expression of CXCR4 and other surface markers on classical, intermediate, and non-classical monocytes in women.Methods and resultssCVD was defined as presence of atherosclerotic lesions in the carotid artery in 92 participants of the Women’s Interagency HIV Study (WIHS). Participants were stratified into four sets (n = 23 each) by HIV and sCVD status (HIV−/sCVD−, HIV−/sCVD+, HIV+/sCVD−, and HIV+/sCVD+) matched by age, race/ethnicity, and smoking status. Three subsets of monocytes were determined from archived peripheral blood mononuclear cells. Flow cytometry was used to count and phenotype surface markers. We tested for differences by HIV and sCVD status accounting for multiple comparisons. We found no differences in monocyte subset size among the four groups. Expression of seven surface markers differed significantly across the three monocyte subsets. CXCR4 expression [median fluorescence intensity (MFI)] in non-classical monocytes was highest among HIV−/CVD− [628, interquartile range (IQR) (295–1389)], followed by HIV+/CVD− [486, IQR (248–699)], HIV−/CVD+ (398, IQR (89–901)), and lowest in HIV+/CVD+ women [226, IQR (73–519)), P = 0.006 in ANOVA. After accounting for multiple comparison (Tukey) the difference between HIV−/CVD− vs. HIV+/CVD+ remained significant with P = 0.005 (HIV−/CVD− vs. HIV+/CVD− P = 0.04, HIV−/CVD− vs. HIV−/CVD+ P = 0.06, HIV+/CVD+ vs. HIV+/CVD− P = 0.88, HIV+/CVD+ vs. HIV−/CVD+ P = 0.81, HIV+/CVD− vs. HIV−/CVD+, P = 0.99). All pairwise comparisons with HIV−/CVD− were individually significant (P = 0.050 vs. HIV−/CVD+, P = 0.028 vs. HIV+/CVD−, P = 0.009 vs. HIV+/CVD+). CXCR4 expression on non-classical monocytes was significantly higher in CVD− (501.5, IQR (249.5–887.3)) vs. CVD+ (297, IQR (81.75–626.8) individuals (P = 0.028, n = 46 per group). CXCR4 expression on non-classical monocytes significantly correlated with cardiovascular and HIV−related risk factors including systolic blood pressure, platelet and T cell counts along with duration of antiretroviral therapy (P ConclusionCXCR4 expression in non-classical monocytes was significantly lower among women with both HIV infection and sCVD, suggesting a potential atheroprotective role of CXCR4 in non-classical monocytes.
- Published
- 2018
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