RESUMEN
OBJECTIVE: Angiopoietin-1 (Ang-1), a secreted protein, mainly regulates angiogenesis. Ang-1 has been shown to promote the development of atherosclerosis, whereas little is known about its effects on lipid metabolism and inflammation in this process. METHOD: Ang-1 was transfected into ApoE-/- mice via lentiviral vector or incubated with THP-1 derived macrophages. Oil red O and HE staining were performed to measure the size of atherosclerotic plaques in ApoE-/- mice. Immunofluorescence was employed to show the expression of target proteins in aorta. [3H] labeled cholesterol was performed to examine the efficiency of cholesterol efflux and reverse cholesterol transport (RCT) both in vivo and vitro. Western blot and qPCR were used to quantify target proteins both in vivo and vitro. ELISA detected the levels of pro-inflammatory cytokines in mouse peritoneal macrophage. RESULTS: Our data showed that Ang-1 augmented atherosclerotic plaques formation and inhibited cholesterol efflux. The binding of Ang-1 to Tie2 resulted in downregulation of LXRα, ABCA1 and ABCG1 expression via inhibiting the translocation of TFE3 into nucleus. In addition, Ang-1 decreased serum HDL-C levels and reduced reverse cholesterol transport (RCT) in ApoE-/- mice. Furthermore, Ang-1 induced lipid accumulation followed by increasing TNF-α, IL-6, IL-1ßï¼and MCP-1 produced by MPMs, as well as inducing M1 phenotype macrophage marker iNOS and CD86 expression in aorta of ApoE-/- mice. CONCLUSION: Ang-1 has an adverse effect on cholesterol efflux by decreasing the expression of ABCA1 and ABCG1 via Tie2/TFE3/LXRα pathway, thereby promoting inflammation and accelerating atherosclerosis progression.
Asunto(s)
Angiopoyetina 1/metabolismo , Aterosclerosis/metabolismo , Colesterol/metabolismo , Inflamación/metabolismo , Transducción de Señal/inmunología , Transportador 1 de Casete de Unión a ATP/metabolismo , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 1/metabolismo , Angiopoyetina 1/genética , Animales , Aterosclerosis/inmunología , Aterosclerosis/patología , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Modelos Animales de Enfermedad , Vectores Genéticos/genética , Humanos , Inflamación/inmunología , Inflamación/patología , Lentivirus/genética , Receptores X del Hígado/metabolismo , Masculino , Ratones , Ratones Noqueados para ApoE , Receptor TIE-2/metabolismo , Células THP-1 , TransfecciónRESUMEN
PURPOSE: To investigate the associations of ANLN expression with prognosis of breast cancer and clinical outcome of anthracycline-based chemotherapy. METHODS: This study enrolled 308 breast cancer patients in which 264 of them received anthracycline-based chemotherapy. Immunohistochemistry was used to detect ANLN expression level of the patients. Clinical characteristics of the patients were collected, and associations of ANLN expression with prognosis were analyzed. RESULTS: Our results showed that ANLN expression was associated with survival of breast cancer patients, and it was also related to clinical outcome of patients received anthracycline-based chemotherapy. Breast cancer patients with high expression of ANLN would have poor prognosis and poor clinical outcome to anthracycline-based chemotherapy. CONCLUSION: ANLN could be an independent prognosis predictor for breast cancer, and its expression might be used to predict the anthracycline-based chemotherapy clinical outcome in breast cancer patients.
