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 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.
  
  
  BACKGROUND
  NCT 00455793.
authors.affiliation: Massachusetts General Hospital, Program in Nutritional Metabolism, Harvard Medical School.
authors.forename: Markella V
authors.initials: MV
authors.lastname: Zanni
authors.affiliation: David Geffen School of Medicine, University of California Los Angeles.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Kelesidis
authors.affiliation: Massachusetts General Hospital, Lipid Metabolism Unit, Harvard Medical School.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Fitzgerald
authors.affiliation: Massachusetts General Hospital, Program in Nutritional Metabolism, Harvard Medical School.
authors.forename: Janet
authors.initials: J
authors.lastname: Lo
authors.affiliation: Massachusetts General Hospital, Department of Radiology, Harvard Medical School.
authors.forename: Suhny
authors.initials: S
authors.lastname: Abbara
authors.affiliation: Massachusetts General Hospital, Department of Radiology, Harvard Medical School.
authors.forename: Bryan
authors.initials: B
authors.lastname: Wai
authors.affiliation: Massachusetts General Hospital, Program in Nutritional Metabolism, Harvard Medical School.
authors.forename: Eleni
authors.initials: E
authors.lastname: Marmarelis
authors.affiliation: Massachusetts General Hospital, Lipid Metabolism Unit, Harvard Medical School.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Hernandez
authors.affiliation: David Geffen School of Medicine, University of California Los Angeles.
authors.forename: Otto O
authors.initials: OO
authors.lastname: Yang
authors.affiliation: David Geffen School of Medicine, University of California Los Angeles.
authors.forename: Judith S
authors.initials: JS
authors.lastname: Currier
authors.affiliation: Massachusetts General Hospital, Program in Nutritional Metabolism, Harvard Medical School.
authors.forename: Steven K
authors.initials: SK
authors.lastname: Grinspoon
mesh_terms: D000293:Adolescent; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D003324:Coronary Artery Disease / Q000150:complications*; D015658:HIV Infections / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators; D008055:Lipids / Q000097:blood; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008262:Macrophage Activation; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D058226:Plaque, Atherosclerotic / Q000276:immunology* / Q000378:metabolism*; D012307:Risk Factors; D055815:Young Adult
chemical_list: D018836:Inflammation Mediators; D008055:Lipids; D008075:Lipoproteins, HDL