Perturbations of circulating levels of RANKL-osteoprotegerin axis in relation to lipids and progression of atherosclerosis in HIV-infected and -uninfected adults: ACTG NWCS 332/A5078 Study.

TitlePerturbations of circulating levels of RANKL-osteoprotegerin axis in relation to lipids and progression of atherosclerosis in HIV-infected and -uninfected adults: ACTG NWCS 332/A5078 Study.
Publication TypeJournal Article
Year of Publication2013
AuthorsKelesidis T, Kendall MA, Yang OO, Hodis H, Currier JS
JournalAIDS Res Hum Retroviruses
Volume29
Issue6
Pagination938-48
Date Published2013 Jun
ISSN1931-8405
KeywordsAdult, Atherosclerosis, Case-Control Studies, Disease Progression, Female, HIV Infections, HIV-1, Humans, Lipids, Male, Middle Aged, Osteoprotegerin, Prospective Studies, RANK Ligand, Risk Factors
Abstract

The receptor activator of the NF-κB ligand (RANKL)-osteoprotegerin (OPG) axis has been shown to play a role in the inflammatory process of atherogenesis and may be regulated by changes in levels of cholesterol. However, the interplay between HIV-1 infection, lipids, the RANKL-OPG axis, and atherosclerosis is poorly defined. Serum RANKL, OPG, and RANKL/OPG ratio were retrospectively assessed for 91 subjects from a 3-year study of carotid artery intima-media thickness (CIMT), which enrolled triads of risk factor-matched persons that were HIV-1 uninfected (n=36) or HIV-1(+) with (n=29) or without (n=26) continuous protease inhibitor (PI)-based therapy for ≥2 years. Associations of serum RANKL, OPG, and RANKL/OPG ratio to the primary outcomes of levels of circulating lipids and atherosclerosis progression were determined using multivariate regression models. Serum RANKL and RANKL/OPG ratio were significantly lower in HIV-infected versus HIV-uninfected subjects (p<0.01). Multivariate models for HIV-1(+) subjects, but not in uninfected controls, demonstrated that perturbations in serum cholesterol levels were significantly associated (p<0.05) with perturbations in serum levels of RANKL and OPG, and their ratio (RANKL/OPG). There were no significant associations of serum RANKL, OPG, and RANKL/OPG with progression of atherosclerosis in HIV-1(+) subjects. Our results suggest that HIV-1 infection is associated with reductions in both serum RANKL and the RANKL/OPG ratio, and perturbations in the circulating levels of RANKL and OPG are significantly associated with increases in cholesterol levels, but not with progression of atherosclerosis.

DOI10.1089/AID.2012.0305
Alternate JournalAIDS Res. Hum. Retroviruses
PubMed ID23351153
PubMed Central IDPMC3653400
Grant List5R01HL095126 / HL / NHLBI NIH HHS / United States
AI056933 / AI / NIAID NIH HHS / United States
AI068634 / AI / NIAID NIH HHS / United States
AI28697 / AI / NIAID NIH HHS / United States
U01 AI068634 / AI / NIAID NIH HHS / United States