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.
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.
Department of Medicine, Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, CA 90035, USA.
Theodoros
T
Kelesidis
Michelle A
MA
Kendall
Otto O
OO
Yang
Howard
H
Hodis
Judith S
JS
Currier
D000328:Adult; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology*; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000150:complications*; D015497:HIV-1; D006801:Humans; D008055:Lipids / Q000097:blood* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000097:blood* / Q000502:physiology; D011446:Prospective Studies; D053245:RANK Ligand / Q000097:blood* / Q000502:physiology; D012307:Risk Factors
D008055:Lipids; D053244:Osteoprotegerin; D053245:RANK Ligand