RESUMO
BACKGROUND: Atherosclerosis (AS) is a lipid-driven inflammatory disease of the arterial intima. Evidence is growing that dysregulation of lncRNAs is implicated in the pathogenesis of AS. In this research, the role of lncRNA KCNQ1OT1 in AS was investigated. METHODS: ApoE-/- mice were fed on a high fat diet to establish mouse models of AS. Macrophages (THP-1) were treated with oxidized low-density lipoprotein (ox-LDL) to establish cell models of AS. Atherosclerotic lesions of AS mice were determined by performing Oil red O staining. Lipid metabolic disorders and inflammatory were detected using specific assay kits. KCNQ1OT1 and miR-145-5p expression was measured using RT-qPCR. Levels of PPARα and CPT1 were measured using western blot. RESULTS: KCNQ1OT1 expression was upregulated and miR-145-5p was downregulated in atherosclerotic plaques of AS mice and ox-LDL-treated THP-1 cells. Lipid metabolic disorders and inflammation in vivo and in vitro were attenuated by either KCNQ1OT1 knockdown or miR-145-5p overexpression. Additionally, KCNQ1OT1 acted as a molecular sponge of miR-145-5p and downregulated miR-145-5p expression. Furthermore, silencing miR-145-5p abolished the effect of KCNQ1OT1 knockdown. CONCLUSION: Silencing KCNQ1OT1 attenuates AS progression by sponging miR-145-5p.
Assuntos
Aorta , Doenças da Aorta , Aterosclerose , Inflamação , Macrófagos , MicroRNAs , RNA Longo não Codificante , Animais , Humanos , Masculino , Aorta/efeitos dos fármacos , Aorta/metabolismo , Aorta/patologia , Doenças da Aorta/genética , Doenças da Aorta/metabolismo , Doenças da Aorta/patologia , Doenças da Aorta/prevenção & controle , Aterosclerose/genética , Aterosclerose/metabolismo , Aterosclerose/patologia , Aterosclerose/prevenção & controle , Modelos Animais de Doenças , Progressão da Doença , Regulação da Expressão Gênica , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Inflamação/prevenção & controle , Lipoproteínas LDL/toxicidade , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , MicroRNAs/genética , MicroRNAs/metabolismo , Placa Aterosclerótica , Canais de Potássio de Abertura Dependente da Tensão da Membrana/genética , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Interferência de RNA , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Transdução de Sinais , Células THP-1RESUMO
The aim of this study was to explore the role and regulatory mechanism of microRNA-298 (miR-298) in myocardial ischemic injury. H9c2 cardiomyocytes were cultured under hypoxia (3 % O2) conditions to induce myocardial ischemic injury. Subsequently, the effects of miR-298 overexpression and suppression on hypoxia-induced myocardial damage in H9c2 cells were investigated. Moreover, the target of miR-298 was identified in H9c2 cells and the relationship between miR-298 and the activation of PTEN/PI3K/AKT signaling pathway was explored. miR-298 was upregulated in hypoxia-stimulated H9c2 cells. Overexpression of miR-298 distinctly aggravated hypoxia-induced myocardial damage in hypoxia-treated H9c2 cells, whereas inhibition of miR-298 alleviated hypoxia-induced injury. Moreover, miR-298 negatively regulated the expression of cyclin D1, and cyclin D1 was a target of miR-298 in H9c2 cells. Suppression of cyclin D1 significantly reversed the effects of suppression of miR-298 on hypoxia-induced myocardial damage. Lastly, inhibition of miR-298 activated the PTEN/PI3K/AKT signaling pathway, and this effect could be reversed after suppression of cyclin D1. Our results reveal that miR-298 may exacerbate myocardial ischemic injury by targeting cyclin D1 and regulating the activation of PTEN/PI3K/AKT signaling pathway. miR-298 may serve as a promising targets for reducing myocardial ischemic injury.
Assuntos
Ciclina D1/genética , Ciclina D1/metabolismo , MicroRNAs/metabolismo , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/metabolismo , Hipóxia Celular/genética , Linhagem Celular , MicroRNAs/fisiologia , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de SinaisRESUMO
An analysis of the effects of potential oil spills will provide data in support of decisions related to improving the response to oil spills and its emergency management. We selected the Chinese Bohai Sea, especially the Bohai Strait, as our investigation region to provide an assessment of the effects of pollution from ship-related oil spills on adjacent coastal zones. Ship-related accidents are one of the major factors causing potential oil spills in this area. A three dimensional oil transport and transformation model was developed using the Estuary, Coastal, and Ocean Model. This proposed model was run 90 times and each run lasted for 15days to simulate the spread and weathering processes of oil for each of four potential spill sites, which represented potential sites of ship collisions along heavy traffic lanes in the Bohai Sea. Ten neighboring coastal areas were also considered as target zones that potentially could receive pollutants once oil spilled in the study areas. The statistical simulations showed that spills in winter were much worse than those in summer; they resulted in very negative effects on several specific target zones coded Z7, Z8, Z9, and Z10 in this paper. In addition, sites S3 (near the Penglai city) and S4 (near the Yantai city) were the two most at-risk sites with a significantly high probability of pollution if spills occurred nearby during winter. The results thus provided practical guidelines for local oil spill prevention, as well as an emergency preparedness and response program.