PMID- 30520941 OWN - NLM STAT- MEDLINE DCOM- 20200518 LR - 20220929 IS - 1755-3245 (Electronic) IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 115 IP - 6 DP - 2019 May 1 TI - Loss of CXCR4 on non-classical monocytes in participants of the Women's Interagency HIV Study (WIHS) with subclinical atherosclerosis. PG - 1029-1040 LID - 10.1093/cvr/cvy292 [doi] 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. CI - Published on behalf of the European Society of Cardiology. All rights reserved. (c) The Author(s) 2018. For permissions, please email: journals.permissions@oup.com. FAU - Mueller, Karin A L AU - Mueller KAL AD - La Jolla Institute of Immunology, Athena Circle Drive La Jolla, CA, USA. AD - Eberhard Karls University, Tuebingen University Hospital, Department of Cardiology, Otfried-Mueller-Strasse 10, Tuebingen, Germany. FAU - Hanna, David B AU - Hanna DB AD - Department of Epidemiology and Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Belfer 13th floor, Bronx, NY, USA. FAU - Ehinger, Erik AU - Ehinger E AD - La Jolla Institute of Immunology, Athena Circle Drive La Jolla, CA, USA. FAU - Xue, Xiaonan AU - Xue X AD - Department of Epidemiology and Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Belfer 13th floor, Bronx, NY, USA. FAU - Baas, Livia AU - Baas L AD - La Jolla Institute of Immunology, Athena Circle Drive La Jolla, CA, USA. AD - Eberhard Karls University, Tuebingen University Hospital, Department of Cardiology, Otfried-Mueller-Strasse 10, Tuebingen, Germany. FAU - Gawaz, Meinrad P AU - Gawaz MP AD - Eberhard Karls University, Tuebingen University Hospital, Department of Cardiology, Otfried-Mueller-Strasse 10, Tuebingen, Germany. FAU - Geisler, Tobias AU - Geisler T AD - Eberhard Karls University, Tuebingen University Hospital, Department of Cardiology, Otfried-Mueller-Strasse 10, Tuebingen, Germany. FAU - Anastos, Kathryn AU - Anastos K AD - Department of Epidemiology and Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Belfer 13th floor, Bronx, NY, USA. FAU - Cohen, Mardge H AU - Cohen MH AD - John H. Stroger, Jr. Hospital of Cook County, 1969 Ogden Ave, Chicago, IL, USA. FAU - Gange, Stephen J AU - Gange SJ AD - Department of Epidemiology, Johns Hopkins University, 265 Garland Hall, 3400 North Charles Street, Baltimore, MD, USA. FAU - Heath, Sonya L AU - Heath SL AD - Department of Medicine, University of Alabama at Birmingham, 908 20th Street South, Birmingham, AL, USA. FAU - Lazar, Jason M AU - Lazar JM AD - Department of Medicine, SUNY-Downstate Medical Center, 450 Clarkson Ave, Brooklyn, NY, USA. FAU - Liu, Chenglong AU - Liu C AD - Georgetown University Medical Center, Washington, DC, USA. FAU - Mack, Wendy J AU - Mack WJ AD - Department of Preventive Medicine, University of Southern California, 2001 N Soto St, Los Angeles, CA, USA. FAU - Ofotokun, Igho AU - Ofotokun I AD - Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, 49 Jesse Hill Jr. Drive, Atlanta, GA, USA. FAU - Tien, Phyllis C AU - Tien PC AD - Department of Medicine, VAMC, Infectious Disease Section, 111W 4150 Clement St., San Francisco, CA, USA. FAU - Hodis, Howard N AU - Hodis HN AD - Department of Preventive Medicine, University of Southern California, 2001 N Soto St, Los Angeles, CA, USA. FAU - Landay, Alan L AU - Landay AL AD - Department of Internal Medicine, Rush University Medical Center, 1735 West Harrison St, Chicago, IL, USA. FAU - Kaplan, Robert C AU - Kaplan RC AD - Department of Epidemiology and Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Belfer 13th floor, Bronx, NY, USA. AD - Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. FAU - Ley, Klaus AU - Ley K AD - La Jolla Institute of Immunology, Athena Circle Drive La Jolla, CA, USA. LA - eng GR - P30 AI050409/AI/NIAID NIH HHS/United States GR - U01 AI103397/AI/NIAID NIH HHS/United States GR - U01 AI031834/AI/NIAID NIH HHS/United States GR - U01 AI035004/AI/NIAID NIH HHS/United States GR - P30 AI051519/AI/NIAID NIH HHS/United States GR - R01 HL095140/HL/NHLBI NIH HHS/United States GR - R01 HL083760/HL/NHLBI NIH HHS/United States GR - UL1 TR000454/TR/NCATS NIH HHS/United States GR - U01 AI103401/AI/NIAID NIH HHS/United States GR - UL1 TR000004/TR/NCATS NIH HHS/United States GR - U01 AI103408/AI/NIAID NIH HHS/United States GR - U01 AI034989/AI/NIAID NIH HHS/United States GR - R21 HL120394/HL/NHLBI NIH HHS/United States GR - R01 HL126543/HL/NHLBI NIH HHS/United States GR - U01 AI034994/AI/NIAID NIH HHS/United States GR - R21 AG059505/AG/NIA NIH HHS/United States GR - U01 AI103390/AI/NIAID NIH HHS/United States GR - U01 AI034993/AI/NIAID NIH HHS/United States GR - P30 AI050410/AI/NIAID NIH HHS/United States GR - K01 HL137557/HL/NHLBI NIH HHS/United States GR - U01 HD032632/HD/NICHD NIH HHS/United States GR - U01 AI042590/AI/NIAID NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - England TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (Biomarkers) RN - 0 (CXCR4 protein, human) RN - 0 (Receptors, CXCR4) SB - IM CIN - Cardiovasc Res. 2019 May 1;115(6):989-991. PMID: 30830148 MH - Adult MH - Antiretroviral Therapy, Highly Active MH - Asymptomatic Diseases MH - Biomarkers/analysis MH - Carotid Artery Diseases/diagnosis/*immunology MH - Cross-Sectional Studies MH - Down-Regulation MH - Female MH - HIV Infections/diagnosis/drug therapy/*immunology MH - Humans MH - Middle Aged MH - Monocytes/classification/drug effects/*immunology MH - Phenotype MH - Plaque, Atherosclerotic MH - Receptors, CXCR4/*analysis MH - Sex Factors PMC - PMC6735712 OTO - NOTNLM OT - Atherosclerosis OT - CXCR4 OT - Cardiovascular risk assessment OT - HIV OT - Non-classical monocytes OT - Women EDAT- 2018/12/07 06:00 MHDA- 2020/05/19 06:00 PMCR- 2020/05/01 CRDT- 2018/12/07 06:00 PHST- 2018/05/16 00:00 [received] PHST- 2018/11/07 00:00 [revised] PHST- 2018/12/04 00:00 [accepted] PHST- 2018/12/07 06:00 [pubmed] PHST- 2020/05/19 06:00 [medline] PHST- 2018/12/07 06:00 [entrez] PHST- 2020/05/01 00:00 [pmc-release] AID - 5231867 [pii] AID - cvy292 [pii] AID - 10.1093/cvr/cvy292 [doi] PST - ppublish SO - Cardiovasc Res. 2019 May 1;115(6):1029-1040. doi: 10.1093/cvr/cvy292.