HDL redox activity is increased in HIV-infected men in association with macrophage activation and non-calcified coronary atherosclerotic plaque

Markella V. Zanni, Theodoros Kelesidis, Michael L. Fitzgerald, Janet Lo, Suhny Abbara, Bryan Wai, Eleni Marmarelis, Nicholas J. Hernandez, Otto O. Yang, Judith S. Currier, Steven K. Grinspoon

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Abstract

Background: HIV is associated with atherosclerosis and low high-density lipoprotein (HDL). With inflammation, HDL becomes dysfunctional. We previously showed that proinflammatory HDL has high HDL redox activity (HRA). In this study, we compare HRA in HIV-infected versus non-HIV-infected subjects and relate HRA to indices of macrophage activation and cardiovascular disease risk. Methods: 102 HIV-infected subjects and 41 matched non-HIV controls without clinical cardiovascular disease underwent coronary CT angiography (CTA) and testing for immune/inflammatory biomarkers. The effect of purified HDL from each study subject on the oxidation rate of dihydrorhodamine-123 (DOR) was normalized to the DOR of pooled HDL from healthy subjects. The normalized ratio DOR subject/DOR pooled was used as a measure of HRA, with higher HRA suggesting dysfunctional HDL. Results: HRA was higher in HIV-infected versus non-HIV subjects (1.4 ± 0.01 versus 1.3 ± 0.01, P=0.03). In multivariate modelling for HRA among all subjects, HIV status remained positively related to HRA (P=0.02), even after controlling for traditional cardiovascular risk factors, comorbid conditions and immune activation. Among HIV-infected subjects, HRA correlated inversely with HDL (rho=-0.32, P=0.002) and log adiponectin (r=-0.28, P=0.006), and correlated positively with log sCD163 (r=0.24, P=0.02) - a monocyte/macrophage activation marker - and with the percentage of non-calcified coronary atherosclerotic plaque (r=0.29, P=0.03). sCD163 remained significantly associated with HRA in multivariate modelling among HIV-infected subjects ( P=0.03). Conclusions: These data demonstrate increased HRA among HIV-infected subjects versus matched non-HIV subjects with comparable HDL levels. In HIV-infected subjects, HRA relates to macrophage activation and to noncalcified coronary atherosclerotic plaque, which may be rupture-prone. Further studies are needed in HIV-infected patients to elucidate the interplay between immune activation, HDL function and CVD risk.

Original languageEnglish (US)
Pages (from-to)805-811
Number of pages7
JournalAntiviral Therapy
Volume19
Issue number8
DOIs
StatePublished - 2014

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Macrophage Activation
Atherosclerotic Plaques
HDL Lipoproteins
Oxidation-Reduction
HIV
Cardiovascular Diseases
Adiponectin
Coronary Angiography
LDL Lipoproteins
Rupture
Monocytes
Atherosclerosis
Healthy Volunteers
Biomarkers

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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HDL redox activity is increased in HIV-infected men in association with macrophage activation and non-calcified coronary atherosclerotic plaque. / Zanni, Markella V.; Kelesidis, Theodoros; Fitzgerald, Michael L.; Lo, Janet; Abbara, Suhny; Wai, Bryan; Marmarelis, Eleni; Hernandez, Nicholas J.; Yang, Otto O.; Currier, Judith S.; Grinspoon, Steven K.

In: Antiviral Therapy, Vol. 19, No. 8, 2014, p. 805-811.

Research output: Contribution to journalArticle

Zanni, MV, Kelesidis, T, Fitzgerald, ML, Lo, J, Abbara, S, Wai, B, Marmarelis, E, Hernandez, NJ, Yang, OO, Currier, JS & Grinspoon, SK 2014, 'HDL redox activity is increased in HIV-infected men in association with macrophage activation and non-calcified coronary atherosclerotic plaque', Antiviral Therapy, vol. 19, no. 8, pp. 805-811. https://doi.org/10.3851/IMP2756
Zanni, Markella V. ; Kelesidis, Theodoros ; Fitzgerald, Michael L. ; Lo, Janet ; Abbara, Suhny ; Wai, Bryan ; Marmarelis, Eleni ; Hernandez, Nicholas J. ; Yang, Otto O. ; Currier, Judith S. ; Grinspoon, Steven K. / HDL redox activity is increased in HIV-infected men in association with macrophage activation and non-calcified coronary atherosclerotic plaque. In: Antiviral Therapy. 2014 ; Vol. 19, No. 8. pp. 805-811.
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title = "HDL redox activity is increased in HIV-infected men in association with macrophage activation and non-calcified coronary atherosclerotic plaque",
abstract = "Background: HIV is associated with atherosclerosis and low high-density lipoprotein (HDL). With inflammation, HDL becomes dysfunctional. We previously showed that proinflammatory HDL has high HDL redox activity (HRA). In this study, we compare HRA in HIV-infected versus non-HIV-infected subjects and relate HRA to indices of macrophage activation and cardiovascular disease risk. Methods: 102 HIV-infected subjects and 41 matched non-HIV controls without clinical cardiovascular disease underwent coronary CT angiography (CTA) and testing for immune/inflammatory biomarkers. The effect of purified HDL from each study subject on the oxidation rate of dihydrorhodamine-123 (DOR) was normalized to the DOR of pooled HDL from healthy subjects. The normalized ratio DOR subject/DOR pooled was used as a measure of HRA, with higher HRA suggesting dysfunctional HDL. Results: HRA was higher in HIV-infected versus non-HIV subjects (1.4 ± 0.01 versus 1.3 ± 0.01, P=0.03). In multivariate modelling for HRA among all subjects, HIV status remained positively related to HRA (P=0.02), even after controlling for traditional cardiovascular risk factors, comorbid conditions and immune activation. Among HIV-infected subjects, HRA correlated inversely with HDL (rho=-0.32, P=0.002) and log adiponectin (r=-0.28, P=0.006), and correlated positively with log sCD163 (r=0.24, P=0.02) - a monocyte/macrophage activation marker - and with the percentage of non-calcified coronary atherosclerotic plaque (r=0.29, P=0.03). sCD163 remained significantly associated with HRA in multivariate modelling among HIV-infected subjects ( P=0.03). Conclusions: These data demonstrate increased HRA among HIV-infected subjects versus matched non-HIV subjects with comparable HDL levels. In HIV-infected subjects, HRA relates to macrophage activation and to noncalcified coronary atherosclerotic plaque, which may be rupture-prone. Further studies are needed in HIV-infected patients to elucidate the interplay between immune activation, HDL function and CVD risk.",
author = "Zanni, {Markella V.} and Theodoros Kelesidis and Fitzgerald, {Michael L.} and Janet Lo and Suhny Abbara and Bryan Wai and Eleni Marmarelis and Hernandez, {Nicholas J.} and Yang, {Otto O.} and Currier, {Judith S.} and Grinspoon, {Steven K.}",
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T1 - HDL redox activity is increased in HIV-infected men in association with macrophage activation and non-calcified coronary atherosclerotic plaque

AU - Zanni, Markella V.

AU - Kelesidis, Theodoros

AU - Fitzgerald, Michael L.

AU - Lo, Janet

AU - Abbara, Suhny

AU - Wai, Bryan

AU - Marmarelis, Eleni

AU - Hernandez, Nicholas J.

AU - Yang, Otto O.

AU - Currier, Judith S.

AU - Grinspoon, Steven K.

PY - 2014

Y1 - 2014

N2 - Background: HIV is associated with atherosclerosis and low high-density lipoprotein (HDL). With inflammation, HDL becomes dysfunctional. We previously showed that proinflammatory HDL has high HDL redox activity (HRA). In this study, we compare HRA in HIV-infected versus non-HIV-infected subjects and relate HRA to indices of macrophage activation and cardiovascular disease risk. Methods: 102 HIV-infected subjects and 41 matched non-HIV controls without clinical cardiovascular disease underwent coronary CT angiography (CTA) and testing for immune/inflammatory biomarkers. The effect of purified HDL from each study subject on the oxidation rate of dihydrorhodamine-123 (DOR) was normalized to the DOR of pooled HDL from healthy subjects. The normalized ratio DOR subject/DOR pooled was used as a measure of HRA, with higher HRA suggesting dysfunctional HDL. Results: HRA was higher in HIV-infected versus non-HIV subjects (1.4 ± 0.01 versus 1.3 ± 0.01, P=0.03). In multivariate modelling for HRA among all subjects, HIV status remained positively related to HRA (P=0.02), even after controlling for traditional cardiovascular risk factors, comorbid conditions and immune activation. Among HIV-infected subjects, HRA correlated inversely with HDL (rho=-0.32, P=0.002) and log adiponectin (r=-0.28, P=0.006), and correlated positively with log sCD163 (r=0.24, P=0.02) - a monocyte/macrophage activation marker - and with the percentage of non-calcified coronary atherosclerotic plaque (r=0.29, P=0.03). sCD163 remained significantly associated with HRA in multivariate modelling among HIV-infected subjects ( P=0.03). Conclusions: These data demonstrate increased HRA among HIV-infected subjects versus matched non-HIV subjects with comparable HDL levels. In HIV-infected subjects, HRA relates to macrophage activation and to noncalcified coronary atherosclerotic plaque, which may be rupture-prone. Further studies are needed in HIV-infected patients to elucidate the interplay between immune activation, HDL function and CVD risk.

AB - Background: HIV is associated with atherosclerosis and low high-density lipoprotein (HDL). With inflammation, HDL becomes dysfunctional. We previously showed that proinflammatory HDL has high HDL redox activity (HRA). In this study, we compare HRA in HIV-infected versus non-HIV-infected subjects and relate HRA to indices of macrophage activation and cardiovascular disease risk. Methods: 102 HIV-infected subjects and 41 matched non-HIV controls without clinical cardiovascular disease underwent coronary CT angiography (CTA) and testing for immune/inflammatory biomarkers. The effect of purified HDL from each study subject on the oxidation rate of dihydrorhodamine-123 (DOR) was normalized to the DOR of pooled HDL from healthy subjects. The normalized ratio DOR subject/DOR pooled was used as a measure of HRA, with higher HRA suggesting dysfunctional HDL. Results: HRA was higher in HIV-infected versus non-HIV subjects (1.4 ± 0.01 versus 1.3 ± 0.01, P=0.03). In multivariate modelling for HRA among all subjects, HIV status remained positively related to HRA (P=0.02), even after controlling for traditional cardiovascular risk factors, comorbid conditions and immune activation. Among HIV-infected subjects, HRA correlated inversely with HDL (rho=-0.32, P=0.002) and log adiponectin (r=-0.28, P=0.006), and correlated positively with log sCD163 (r=0.24, P=0.02) - a monocyte/macrophage activation marker - and with the percentage of non-calcified coronary atherosclerotic plaque (r=0.29, P=0.03). sCD163 remained significantly associated with HRA in multivariate modelling among HIV-infected subjects ( P=0.03). Conclusions: These data demonstrate increased HRA among HIV-infected subjects versus matched non-HIV subjects with comparable HDL levels. In HIV-infected subjects, HRA relates to macrophage activation and to noncalcified coronary atherosclerotic plaque, which may be rupture-prone. Further studies are needed in HIV-infected patients to elucidate the interplay between immune activation, HDL function and CVD risk.

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