TY - JOUR
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.
N1 - Publisher Copyright:
©2014 International Medical Press
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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U2 - 10.3851/IMP2756
DO - 10.3851/IMP2756
M3 - Article
C2 - 24535655
AN - SCOPUS:84907265625
SN - 1359-6535
VL - 19
SP - 805
EP - 811
JO - Antiviral Therapy
JF - Antiviral Therapy
IS - 8
ER -