HIV Protease Inhibitor Ritonavir Impairs Endothelial Function Via Reduction in Adipose Mass and Endothelial Leptin Receptor-Dependent Increases in NADPH Oxidase 1 (Nox1), C-C Chemokine Receptor Type 5 (CCR5), and Inflammation.

ABSTRACT: Background Cardiovascular disease is currently the leading cause of death in patients with human immunodeficiency virus on combination antiretroviral therapy. Although the use of the protease inhibitor ritonavir has been associated with increased prevalence of cardiovascular disease, the underlying mechanisms remain ill-defined. Herein, we tested the hypothesis that ritonavir-mediated lipoatrophy causes endothelial dysfunction via reducing endothelial leptin signaling. Methods and Results Long-term (4 weeks) but not short-term (3 days) treatment with ritonavir reduced body weight, fat mass, and leptin levels and induced endothelial dysfunction in mice. Moreover, ritonavir increased vascular NADPH oxidase 1, aortic H₂O₂ levels as well as interleukin-1β, GATA3 (GATA bin

SUBMITTER: Bruder-Nascimento T 

PROVIDER: S-EPMC7792423 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature