Hdl Redox Activity is Increased in HIV-Infected Men in Association with Macrophage Activation and Non-Calcified Coronary Atherosclerotic Plaque. Issue 8 (November 2014)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Antiviral therapy. Volume 19:Issue 8(2014)
• Page Start: 805
• Page End: 811
• Publication Date: 2014-11
• Subjects: Antiviral agents -- Periodicals; Antiviral Agents -- therapeutic use; Virus Diseases -- therapy; Viruses -- drug effects; Antiviral agents; Periodical; Electronic journals; Periodicals; 616.9106
• DOI: 10.3851/IMP2756
• Languages: English
• ISSNs: 1359-6535

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.