RESUMEN
Atherosclerosis is one of the most common vascular disorders. Endothelial cell (EC) dysfunction and vascular smooth muscle cell (VSMC) proliferation contributes to the development of atherosclerosis. Long non-coding RNAs (lncRNAs) have been implicated in several biological processes and human diseases. Here we show that lncRNA-RNCR3 is expressed in ECs and VSMCs. RNCR3 expression is significantly upregulated in mouse and human aortic atherosclerotic lesions, and cultured ECs and VSMCs upon ox-LDL treatment in vitro. RNCR3 knockdown accelerates the development of atherosclerosis, aggravates hypercholesterolemia and inflammatory factor releases, and decreases EC and VSMC proliferation in vivo. RNCR3 knockdown also reduces the proliferation and migration, and accelerates apoptosis development of EC and VSMC in vitro. RNCR3 acts as a ceRNA, and forms a feedback loop with Kruppel-like factor 2 and miR-185-5p to regulate cell function. This study reveals that RNCR3 has an atheroprotective role in atherosclerosis, and its intervention is a promising strategy for treating atherosclerosis-related vascular dysfunction.
Asunto(s)
Aterosclerosis/genética , Aterosclerosis/fisiopatología , Endotelio Vascular/patología , Endotelio Vascular/fisiopatología , MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , Animales , Aorta/patología , Aterosclerosis/patología , Comunicación Celular , Exosomas/metabolismo , Técnicas de Silenciamiento del Gen , Humanos , Hipercolesterolemia/genética , Hipercolesterolemia/patología , Mediadores de Inflamación/metabolismo , Masculino , Ratones Endogámicos C57BL , MicroARNs/genética , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/patología , ARN Largo no Codificante/genética , Retina/metabolismo , Retina/patología , Regulación hacia Arriba/genéticaRESUMEN
The gut mucosa is an important site of HIV immunopathogenesis with severe depletion of CD4+ T cells occurring during acute infection. The effect of prolonged anti-retroviral therapy (ART) on cycling and restoration of T lymphocytes in the gut remains unclear. Colon and terminal ileal biopsies and peripheral blood samples were collected from viremic, untreated, HIV-infected participants, patients treated with prolonged ART (>5 years), and uninfected controls and analyzed by flow cytometry. In the gut, the proportion of cycling T cells decreased and the number of CD4+ T cells normalized in treated patients in parallel with beta 7 expression on CD4+ T cells in blood. Cycling of gut T cells in viremic patients was associated with increased plasma LPS levels, but not colonic HIV-RNA. These data suggest that gut T-cell activation and microbial translocation may be interconnected whereas prolonged ART may decrease activation and restore gut CD4+ T cells.