Title | HDL redox activity is increased in HIV-infected men in association with macrophage activation and non-calcified coronary atherosclerotic plaque. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Zanni MV, Kelesidis T, Fitzgerald ML, Lo J, Abbara S, Wai B, Marmarelis E, Hernandez NJ, Yang OO, Currier JS, Grinspoon SK |
Journal | Antivir Ther |
Volume | 19 |
Issue | 8 |
Pagination | 805-811 |
Date Published | 2014 |
ISSN | 2040-2058 |
Keywords | Adolescent, Adult, Antiretroviral Therapy, Highly Active, Coronary Artery Disease, HIV Infections, Humans, Inflammation Mediators, Lipids, Lipoproteins, HDL, Macrophage Activation, Male, Middle Aged, Oxidation-Reduction, Plaque, Atherosclerotic, Risk Factors, Young Adult |
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 non-calcified 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. CLINICAL TRIAL REGISTRATION NUMBER: NCT 00455793. |
DOI | 10.3851/IMP2756 |
Alternate Journal | Antivir. Ther. (Lond.) |
PubMed ID | 24535655 |
PubMed Central ID | PMC4423391 |
Grant List | K23 HL092792 / HL / NHLBI NIH HHS / United States M01 RR001066 / RR / NCRR NIH HHS / United States 5R01HL095126 / HL / NHLBI NIH HHS / United States AI068634 / AI / NIAID NIH HHS / United States M01-RR-01066 / RR / NCRR NIH HHS / United States R01 HL095126 / HL / NHLBI NIH HHS / United States K08 AI108272 / AI / NIAID NIH HHS / United States U01 AI068634 / AI / NIAID NIH HHS / United States R01HL095123 / HL / NHLBI NIH HHS / United States UL1 RR025758 / RR / NCRR NIH HHS / United States R01HL112661 / HL / NHLBI NIH HHS / United States KL2 TR000168 / TR / NCATS NIH HHS / United States P30DK040561 / DK / NIDDK NIH HHS / United States K24 AI056933 / AI / NIAID NIH HHS / United States AI28697 / AI / NIAID NIH HHS / United States P30 AI028697 / AI / NIAID NIH HHS / United States R01 HL112661 / HL / NHLBI NIH HHS / United States P30 DK040561 / DK / NIDDK NIH HHS / United States AI056933 / AI / NIAID NIH HHS / United States R01 HL095123 / HL / NHLBI NIH HHS / United States K24 DK064545 / DK / NIDDK NIH HHS / United States 8KL2TR000168-05 / TR / NCATS NIH HHS / United States 1 UL1 RR 025758-01 / RR / NCRR NIH HHS / United States UM1 AI068634 / AI / NIAID NIH HHS / United States |
Submitted by api_import on December 20, 2019 - 1:39pm