TY - JOUR
T1 - Loss of CXCR4 on non-classical monocytes in participants of the Women's Interagency HIV Study (WIHS) with subclinical atherosclerosis
AU - Mueller, Karin A.L.
AU - Hanna, David B.
AU - Ehinger, Erik
AU - Xue, Xiaonan
AU - Baas, Livia
AU - Gawaz, Meinrad P.
AU - Geisler, Tobias
AU - Anastos, Kathryn
AU - Cohen, Mardge H.
AU - Gange, Stephen J.
AU - Heath, Sonya L.
AU - Lazar, Jason M.
AU - Liu, Chenglong
AU - Mack, Wendy J.
AU - Ofotokun, Igho
AU - Tien, Phyllis C.
AU - Hodis, Howard N.
AU - Landay, Alan L.
AU - Kaplan, Robert C.
AU - Ley, Klaus
N1 - Funding Information:
Data in this manuscript were collected by the Women's Interagency HIV Study (WIHS). The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH). WIHS (Principal Investigators): UAB-MS WIHS (Mirjam-Colette Kempf and Deborah Konkle-Parker), U01-AI-103401; Atlanta WIHS (Ighovwerha Ofotokun and Gina Wingood), U01-AI-103408; Bronx WIHS (Kathryn Anastos), U01-AI-035004; Brooklyn WIHS (Howard Minkoff and Deborah Gustafson), U01-AI-031834; Chicago WIHS (Mardge Cohen and Audrey French), U01-AI-034993; Metropolitan Washington WIHS (Seble Kassaye), U01-AI-034994; Miami WIHS (Margaret Fischl and Lisa Metsch), U01-AI-103397; UNC WIHS (Adaora Adimora), U01-AI-103390; Connie Wofsy Women's HIV Study, Northern California (Ruth Greenblatt, Bradley Aouizerat, and Phyllis Tien), U01-AI-034989; WIHS Data Management and Analysis Center (Stephen Gange and Elizabeth Golub), U01-AI-042590; Southern California WIHS (Joel Milam), U01-HD-032632 (WIHS I-WIHS IV). The WIHS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), with additional co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Cancer Institute (NCI), the National Institute on Drug Abuse (NIDA), and the National Institute on Mental Health (NIMH). Targeted supplemental funding for specific projects is also provided by the National Institute of Dental and Craniofacial Research (NIDCR), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute on Deafness and other Communication Disorders (NIDCD), and the NIH Office of Research on Women's Health. WIHS data collection is also supported by UL1-TR000004 (UCSF CTSA), UL1-TR000454 (Atlanta CTSA), and P30-AI-050410 (UNC CFAR). We thank Ms Cornelia Fiessler for excellent statistical supervision. Conflict of interest: none declared.
Publisher Copyright:
© The Author(s) 2018.
PY - 2019/5/1
Y1 - 2019/5/1
N2 - Aims: To 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 results: sCVD 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 < 0.05). In regression analyses, adjusted for education level, study site, and injection drug use, presence of HIV infection and sCVD remained significantly associated with lower CXCR4 expression on non-classical monocytes (P= 0.003), but did not differ in classical or intermediate monocytes. Conclusion: CXCR4 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.
AB - Aims: To 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 results: sCVD 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 < 0.05). In regression analyses, adjusted for education level, study site, and injection drug use, presence of HIV infection and sCVD remained significantly associated with lower CXCR4 expression on non-classical monocytes (P= 0.003), but did not differ in classical or intermediate monocytes. Conclusion: CXCR4 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.
KW - Atherosclerosis
KW - CXCR4
KW - Cardiovascular risk assessment
KW - HIV
KW - Non-classical monocytes
KW - Women
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U2 - 10.1093/cvr/cvy292
DO - 10.1093/cvr/cvy292
M3 - Article
C2 - 30520941
AN - SCOPUS:85065948190
SN - 0008-6363
VL - 115
SP - 1029
EP - 1040
JO - Cardiovascular research
JF - Cardiovascular research
IS - 6
ER -
