RESUMEN
Activation of the silent mating type information regulation 2 homolog 1 (SIRT1) has been shown consistent antiinflammatory function. However, little information is available on the function of SIRT1 during Angiotensin II (AngII)-induced atherosclerosis. Here we report atheroprotective effects of sirt1 activation in a model of AngII-accelerated atherosclerosis, characterized by suppression pro-inflammatory transcription factors Nuclear transcription factor (NF)-κB and Signal Transducers and Activators of Transcription. (STAT) signaling pathway, and atherosclerotic lesion macrophage content. In this model, administration of the SIRT1 agonist SRT1720 substantially attenuated AngII-accelerated atherosclerosis with decreasing blood pressure and inhibited NF-κB and STAT3 activation, which was associated with suppression of inflammatory factor and atherogenic gene expression in the artery. In vitro studies demonstrated similar changes in AngII-treated VSMCs and macrophages: SIRT1 activation inhibited the expression levels of proinflammatory factor. These studies uncover crucial proinflammatory mechanisms of AngII and highlight actions of SIRT1 activation to inhibit AngII signaling, which is atheroprotective.
Asunto(s)
Angiotensina II/metabolismo , Apolipoproteínas E/deficiencia , Aterosclerosis/prevención & control , Compuestos Heterocíclicos de 4 o más Anillos/farmacología , Sirtuina 1/metabolismo , Angiotensina II/administración & dosificación , Animales , Apolipoproteínas E/genética , Aterosclerosis/patología , Aterosclerosis/fisiopatología , Mediadores de Inflamación/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Ratones , Ratones Noqueados , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Interferente Pequeño/genética , Transducción de Señal/efectos de los fármacos , Sirtuina 1/antagonistas & inhibidores , Sirtuina 1/genéticaRESUMEN
AIM: The aim of the present study was to explore the immunologic mechanism of delaying senescence by Strengthening Vital Energy(SVE), Tonifying Kidney (TK) and combined TK and SVE. METHODS: Mice of 20 months were used as senescence model. The effects of the prescriptions on anti-CD3 antibody-induced NF-kappaB activity and the expression of NF-kappaB in T cells from aged mice were analyzed by electrophoretic mobility shift assay (EMSA) and Western blot, respectively. RESULTS: NF-kappaB activity in anti-CD3 antibody-induced T cells from the aged mice was lower than that from young ones. The three prescriptions raised the activity of NF-kappaB in the T cells from the aged mice to certain extent. Combined TK and SVE had no influence on p65 and p50 subunits expressions. CONCLUSION: The increased NF-kappaB activity may be one of mechanisms underlying the improvement of immune response in aged mice by Chinese medicines.