RESUMEN
BACKGROUND: Hyperinsulinemia and insulin resistance have been recently recognized as an important cause of atherosclerosis. Clinical studies have also found that expression of the estrogen receptor is closely related to the incidence of atherosclerosis. This study investigate the effects of insulin and estrogen receptor α (ER-α) in atherosclerosis. METHODS: Double knockout ApoE/Lepr mice were given intraperitoneal injections of insulin, and their aortae were harvested for hematoxylin-eosin staining and immunohistochemical analysis. In addition, vascular smooth muscle cells (VSMCs) were treated with insulin or infected with a lentivirus encoding exogenous ER-α, and changes in gene expression were detected by real-time polymerase chain reaction and western blotting. The methylation levels of the ER-α gene were tested using bisulfite sequencing PCR, and flow cytometry and EdU assay were used to measure VSMCs proliferation. RESULTS: Our results showed that insulin can induce the formation of atherosclerosis. Gene expression analysis revealed that insulin promotes the expression of DNA methyltransferases and inhibits ER-α expression, while 5-aza-2'-deoxycytidine can inhibit this effect of insulin. Bisulfite sequencing PCR analysis showed that methylation of the ER-α second exon region increased in VSMCs treated with insulin. The results also showed that ER-α can inhibit VSMCs proliferation. CONCLUSIONS: Our data suggest that insulin promotes the expression of DNA methyltransferases, induces methylation of ER-α second exon region and decreases the expression of ER-α, thereby interfering with estrogen regulation of VSMCs proliferation, resulting in atherosclerosis.
Asunto(s)
Enfermedades de la Aorta/metabolismo , Aterosclerosis/metabolismo , Metilación de ADN , Receptor alfa de Estrógeno/efectos de los fármacos , Insulina/toxicidad , Músculo Liso Vascular/efectos de los fármacos , Miocitos del Músculo Liso/efectos de los fármacos , Animales , Aorta/efectos de los fármacos , Aorta/metabolismo , Aorta/patología , Enfermedades de la Aorta/inducido químicamente , Enfermedades de la Aorta/genética , Enfermedades de la Aorta/patología , Apolipoproteínas E/deficiencia , Apolipoproteínas E/genética , Aterosclerosis/inducido químicamente , Aterosclerosis/genética , Aterosclerosis/patología , Línea Celular , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Receptor alfa de Estrógeno/genética , Receptor alfa de Estrógeno/metabolismo , Exones , Femenino , Predisposición Genética a la Enfermedad , Ratones Noqueados , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Fenotipo , Ratas , Receptores de Leptina/genética , Receptores de Leptina/metabolismo , Factores de Tiempo , TransfecciónRESUMEN
The treatment of bone infections has always been difficult. The emergence of drug-resistant bacteria has led to a steady decline in the effectiveness of antibiotics. It is also especially important to fight bacterial infections while repairing bone defects and cleaning up dead bacteria to prevent biofilm formation. The development of biomedical materials has provided us with a research direction to address this issue. We aimed to review the current literature, and have summarized multifunctional antimicrobial materials that have long-lasting antimicrobial capabilities that promote angiogenesis, bone production, or "killing and releasing." This review provides a comprehensive summary of the use of biomedical materials in the treatment of bone infections and a reference thereof, as well as encouragement to perform further research in this field.