Loss of CXCR4 on non-classical monocytes in participants of the Women's Interagency HIV Study (WIHS) with subclinical atherosclerosis

Karin A.L. Mueller, David B. Hanna, Erik Ehinger, Xiaonan Xue, Livia Baas, Meinrad P. Gawaz, Tobias Geisler, Kathryn Anastos, Mardge H. Cohen, Stephen J Gange, Sonya L. Heath, Jason M. Lazar, Chenglong Liu, Wendy J. Mack, Igho Ofotokun, Phyllis C. Tien, Howard N. Hodis, Alan L. Landay, Robert C. Kaplan, Klaus Ley

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1029-1040
Number of pages12
JournalCardiovascular research
Volume115
Issue number6
DOIs
StatePublished - May 1 2019

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Monocytes
Atherosclerosis
HIV
Cardiovascular Diseases
Virus Diseases
Blood Cells
Blood Pressure

Keywords

  • Atherosclerosis
  • Cardiovascular risk assessment
  • CXCR4
  • HIV
  • Non-classical monocytes
  • Women

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Loss of CXCR4 on non-classical monocytes in participants of the Women's Interagency HIV Study (WIHS) with subclinical atherosclerosis. / Mueller, Karin A.L.; Hanna, David B.; Ehinger, Erik; Xue, Xiaonan; Baas, Livia; Gawaz, Meinrad P.; Geisler, Tobias; Anastos, Kathryn; Cohen, Mardge H.; Gange, Stephen J; Heath, Sonya L.; Lazar, Jason M.; Liu, Chenglong; Mack, Wendy J.; Ofotokun, Igho; Tien, Phyllis C.; Hodis, Howard N.; Landay, Alan L.; Kaplan, Robert C.; Ley, Klaus.

In: Cardiovascular research, Vol. 115, No. 6, 01.05.2019, p. 1029-1040.

Research output: Contribution to journalArticle

Mueller, KAL, Hanna, DB, Ehinger, E, Xue, X, Baas, L, Gawaz, MP, Geisler, T, Anastos, K, Cohen, MH, Gange, SJ, Heath, SL, Lazar, JM, Liu, C, Mack, WJ, Ofotokun, I, Tien, PC, Hodis, HN, Landay, AL, Kaplan, RC & Ley, K 2019, 'Loss of CXCR4 on non-classical monocytes in participants of the Women's Interagency HIV Study (WIHS) with subclinical atherosclerosis', Cardiovascular research, vol. 115, no. 6, pp. 1029-1040. https://doi.org/10.1093/cvr/cvy292
Mueller, Karin A.L. ; Hanna, David B. ; Ehinger, Erik ; Xue, Xiaonan ; Baas, Livia ; Gawaz, Meinrad P. ; Geisler, Tobias ; Anastos, Kathryn ; Cohen, Mardge H. ; Gange, Stephen J ; Heath, Sonya L. ; Lazar, Jason M. ; Liu, Chenglong ; Mack, Wendy J. ; Ofotokun, Igho ; Tien, Phyllis C. ; Hodis, Howard N. ; Landay, Alan L. ; Kaplan, Robert C. ; Ley, Klaus. / Loss of CXCR4 on non-classical monocytes in participants of the Women's Interagency HIV Study (WIHS) with subclinical atherosclerosis. In: Cardiovascular research. 2019 ; Vol. 115, No. 6. pp. 1029-1040.
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abstract = "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.",
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author = "Mueller, {Karin A.L.} and Hanna, {David B.} and Erik Ehinger and Xiaonan Xue and Livia Baas and Gawaz, {Meinrad P.} and Tobias Geisler and Kathryn Anastos and Cohen, {Mardge H.} and Gange, {Stephen J} and Heath, {Sonya L.} and Lazar, {Jason M.} and Chenglong Liu and Mack, {Wendy J.} and Igho Ofotokun and Tien, {Phyllis C.} and Hodis, {Howard N.} and Landay, {Alan L.} and Kaplan, {Robert C.} and Klaus Ley",
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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

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 - Cardiovascular risk assessment

KW - CXCR4

KW - HIV

KW - Non-classical monocytes

KW - Women

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