HDL Redox Activity is Elevated in HIV+ Subjects in Association with Immune Activation and Parameters of Cardiometabolic Risk

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 723-745-Lipids: Fatty Liver Disease & Lipodystrophies
Basic/Clinical
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-732
Markella V. Zanni*1, Theodoros Kelesidis2, Michael Fitzgerald1, Janet Lo1, Suhny Abbara1, Bryan Wai1, Eleni Marmarelis1, Nicholas Hernandez1, Otto O. Yang2, Judith S. Currier2 and Steven Grinspoon1
1Massachusetts General Hospital, Harvard Medical School, 2David Geffen School of Medicine, UCLA
Background:  HIV is associated with atherosclerosis [1] and dyslipidemia characterized by low HDL [2].  Basic and clinical studies suggest HDL function is altered in an inflammatory milieu such that this typically anti-oxidant/anti-inflammatory molecule takes on pro-oxidant/pro-inflammatory properties [3] [4]. We previously showed that pro-inflammatory HDL has high HDL redox activity (HRA) [5].  Aims of this study were to: 1) compare HRA in HIV+ subjects and non-HIV controls and 2) relate HRA among HIV+ subjects to measures of immune and cardiometabolic dysregulation.

Methods: 102 HIV+ subjects and 41 non-HIV controls without clinical CVD underwent metabolic/immune phenotyping and coronary CT angiography (for assessment of subclinical atherosclerosis)[6]. HRA was determined using a validated fluorometric biochemical assay measuring the effect of purified HDL from subject cryopreserved serum on the rate of oxidation of dihydrorhodamine 123 (DOR)[5]. The DOR value for 1.25 ug of HDL cholesterol from each subject (measured in fluorescence units/minute) was normalized to the DOR of HDL from pooled serum of healthy blood bank donors. The ratio DORsubject/DORpooled was used as a measure of HRA, with higher HRA suggesting dysfunctional HDL.

Results:  The HIV+ and non-HIV groups were well-matched on traditional CVD risk factors. 95% of HIV+ subjects were on ART.  HRA was significantly higher in the HIV+ group versus the non-HIV group (1.4 ± 0.01 vs. 1.3 ± 0.01, p=0.03). Among the entire cohort, HRA correlated inversely with log-transformed HDL levels (r=-0.31, p=0.0002).  HRA among HIV+ subjects correlated negatively with log-transformed adiponectin levels (r=-0.28, p=0.006) and positively with log-transformed levels of the macrophage activation marker soluble CD163 (r=0.24, p=0.02). With respect to cardiometabolic risk parameters, HRA associated positively with log HOMA-IR among non-diabetic HIV+ subjects (r=0.34, p=0.005) and with the percentage of non-calcified coronary plaque among all HIV+ subjects (r=0.29, p=0.03).

Conclusions: These data are the first to show increased HRA among HIV+ subjects on ART  vs. matched non-HIV subjects with comparable HDL levels.  Among HIV+ subjects, HRA is associated with measures of immune and cardiometabolic dysregulation, including levels of sCD163, log HOMA-IR, and percent non-calcified coronary plaque.  Further studies are needed to confirm the utility of HRA as a biomarker for cardiometabolic risk among HIV+ patients.

1. Lo J, Abbara S, Shturman L, et al. Increased prevalence of subclinical coronary atherosclerosis detected by coronary computed tomography angiography in HIV-infected men. AIDS 2010; 24:243-53. 2. Riddler SA, Smit E, Cole SR, et al. Impact of HIV infection and HAART on serum lipids in men. Jama 2003; 289:2978-82. 3. Van Lenten BJ, Hama SY, de Beer FC, et al. Anti-inflammatory HDL becomes pro-inflammatory during the acute phase response. Loss of protective effect of HDL against LDL oxidation in aortic wall cell cocultures. J Clin Invest 1995; 96:2758-67. 4. Morgantini C, Natali A, Boldrini B, et al. Anti-inflammatory and antioxidant properties of HDLs are impaired in type 2 diabetes. Diabetes 2011; 60:2617-23. 5. Kelesidis T, Currier JS, Huynh D, et al. A biochemical fluorometric method for assessing the oxidative properties of HDL. J Lipid Res 2011; 52:2341-51. 6. Burdo TH, Lo J, Abbara S, et al. Soluble CD163, a novel marker of activated macrophages, is elevated and associated with noncalcified coronary plaque in HIV-infected patients. J Infect Dis 2011; 204:1227-36.

Disclosure: SG: Principal Investigator, Bristol-Myers Squibb. Nothing to Disclose: MVZ, TK, MF, JL, SA, BW, EM, NH, OOY, JSC

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Work on this study was funded in part by grants from BMS and from the NIH (R01 HL 095123).