Immune activation, immunosenescence, and osteoprotegerin as markers of endothelial dysfunction in subclinical HIV-associated atherosclerosis.
HIV-infected patients have a significantly greater risk of cardiovascular disease. Several markers including osteoprotegerin have been shown to be involved in the development and progression of atherosclerosis. We investigated the relationship between T-cell phenotype, osteoprotegerin, and atherosclerosis evaluated by carotid intima-media thickness (c-IMT) in 94 HIV+ patients on suppressive antiretroviral therapy with Framingham score <10%. As for the control group, 24 HIV-negative subjects were enrolled. c-IMT was assessed by ultrasound. CD4+/CD8+ T-cell activation (CD38+ HLADR+) and senescence (CD57+ CD28-) were measured by flow cytometry. IL-6 and OPG levels were measured by ELISA kit. c-IMT was higher in HIV+ than in controls. Among HIV+ patients, 44.7% had pathological c-IMT (≥0.9 mm). CD8+ T-cell activation and senescence and OPG plasma levels were higher in HIV+ patients than in controls. Subjects with pathological c-IMT exhibited higher CD8+ immune activation and immunosenescence and OPG levels than subjects with normal c-IMT. Multivariate analysis showed that age, CD8+ CD38+ HLADR+, and CD8+ CD28- CD57+ were independently associated with pathological c-IMT. Several factors have been implicated in the pathogenesis of atherosclerosis in HIV patients. Immune activation and immunosenescence of CD8+ T cell together with OPG plasma levels might be associated with the development and progression of early atherosclerosis, even in the case of viral suppression.
Department of Public Health and Infectious Diseases, " Sapienza" University of Rome, Viale del Policlinico 155, 00161 Rome, Italy.
Alessandra
A
D'Abramo
Department of Public Health and Infectious Diseases, " Sapienza" University of Rome, Viale del Policlinico 155, 00161 Rome, Italy.
Maria Antonella
MA
Zingaropoli
Department of Public Health and Infectious Diseases, " Sapienza" University of Rome, Viale del Policlinico 155, 00161 Rome, Italy.
Alessandra
A
Oliva
Department of Public Health and Infectious Diseases, " Sapienza" University of Rome, Viale del Policlinico 155, 00161 Rome, Italy.
Claudia
C
D'Agostino
Department of Public Health and Infectious Diseases, " Sapienza" University of Rome, Viale del Policlinico 155, 00161 Rome, Italy.
Samir
S
Al Moghazi
Department of Public Health and Infectious Diseases, " Sapienza" University of Rome, Viale del Policlinico 155, 00161 Rome, Italy.
Giulia
G
De Luca
Department of Public Health and Infectious Diseases, " Sapienza" University of Rome, Viale del Policlinico 155, 00161 Rome, Italy.
Marco
M
Iannetta
Department of Public Health and Infectious Diseases, " Sapienza" University of Rome, Viale del Policlinico 155, 00161 Rome, Italy.
Claudio Maria
CM
Mastroianni
Department of Public Health and Infectious Diseases, " Sapienza" University of Rome, Viale del Policlinico 155, 00161 Rome, Italy.
Vincenzo
V
Vullo
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D050197:Atherosclerosis / Q000209:etiology* / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D059168:Carotid Intima-Media Thickness; D016022:Case-Control Studies; D016922:Cellular Senescence / Q000276:immunology; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000097:blood*
D019380:Anti-HIV Agents; D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6; D053244:Osteoprotegerin; C506030:TNFRSF11B protein, human