RESUMEN
Thoracic aortic dissection (TAD) is a severe cardiovascular disease attributed to the abnormal phenotypic switch of vascular smooth muscle cells (VSMCs). We found that the RNA-binding protein PUM2 and the fibulin protein EFEMP1 were significantly decreased at the TAD anatomical site. Therefore, we constructed expression and silencing vectors for PUM2 and EFEMP1 to analyze differential expression. Overexpression of PUM2 inhibited VSMC proliferation and migration. Western blot analysis indicated that PUM2 overexpression in VSMCs upregulated α-SMA and SM22α and downregulated OPN and MMP2. Immunofluorescence demonstrated that PUM2 and EFEMP1 were co-expressed in VSMCs. Immunoprecipitation confirmed that PUM2 bound to EFEMP1 mRNA to promote EFEMP1 expression. An Ang-II-induced aortic dissection mouse model showed that PUM2 impedes the development of aortic dissection in vivo. Our study demonstrates that PUM2 inhibits the VSMC phenotypic switch to prevent aortic dissection by targeting EFEMP1 mRNA. These findings could assist the development of targeted therapy for TAD.
Asunto(s)
Disección Aórtica , Disección de la Aorta Torácica , Ratones , Animales , Células Cultivadas , Disección Aórtica/genética , ARN Mensajero/metabolismo , Miocitos del Músculo Liso/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismoRESUMEN
BACKGROUND: Stanford type A aortic dissection (T(A)AD) is one of the most dangerous cardiovascular diseases and morbid obesity is associated with the prognosis of many cardiovascular diseases. The aim of this study is to investigate the impact of morbid obesity on in-hospital mortality, total hospital costs and discover the prevalence of morbid obesity among inpatients with T(A)AD. METHODS: Patients with a primary diagnosis of T(A)AD were identified from the National Inpatient Sample database (NIS) from 2008 to 2017. These patients were categorized into non-obesity, obesity and morbid obesity. Multivariable regression models were utilized to assess the association between obesity/morbid obesity and in-hospital mortality, total cost and other clinical factors. The temporal trend in prevalence of obesity/morbid obesity in T(A)ADs and the trend of in-hospital mortality among different weight categories were also explored. RESULTS: From the NIS database 8489 T(A)AD inpatients were identified, of which 7230 (85.2%) patients were non-obese, 822 (9.7%) were obese and 437 (5.1%) were morbid obese. Morbid obesity was associated with increased risk of in-hospital mortality (odds ratio [OR] 1.39; 95% confidence interval [CI] 1.03-1.86), 8% higher total cost compared with the non-obese patients. From 2008 to 2017, the rate of obesity and morbid obesity in patients with T(A)AD have significantly increased from 7.36 to 11.33% (P < 0.001) and from 1.95 to 7.37% (P < 0.001). Factors associated with morbid obesity in T(A)ADs included age, female, elective admission, hospital region, dyslipidemia, smoking, rheumatoid arthritis/collagen vascular diseases, chronic pulmonary disease, diabetes and hypertension. CONCLUSIONS: Morbid obesity are connected with worse clinical outcomes and more health resource utilization in T(A)AD patients. Appropriate medical resource orientation and weight management education for T(A)AD patients may be necessary.