PUM2 regulates the formation of thoracic aortic dissection through EFEMP1.

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.

A novel arterial coupler with non-return snap-fit connection approach optimized arterial end-to-end anastomotic technique: An experimental study.

PURPOSE: Hand-sewn anastomosis as the gold standard of vascular anastomosis cannot fully meet the requirements of vascular anastomosis in speed and quality. Various vascular couplers have been developed to ameliorate this situation. Most of them are mainly used for venous anastomosis rather than arterial anastomosis, even though it is generally acknowledged that in almost all operations involving vascular reconstruction, it is the arteries that need to be anastomosed faster and more accurately and not the veins. A dedicated device is needed for creating arterial anastomosis in an easy, timesaving, less damaging but reliable procedure. Therefore, we plan to develop a novel arterial coupler device and test pre-clinical safety and effectiveness. METHODS: In this cohort study, the rationality of this novel arterial coupler was preliminarily tested by finite element analysis before it was manufactured. Several factors restrict the use of vascular couplers in arterial anastomosis, such as arterial eversion, fixation, etc. The manufactured arterial couplers underwent in vitro and in vivo experiments. In vitro, isolated arteries of beagles were anastomosed with the assistance of an arterial coupler, and the anastomosed arteries were evaluated through anti-traction tests. In animal experiments, the bilateral femoral arteries of 5 beagles served as a control group. After dissection, the femoral artery on one side was randomly selected to be anastomosed with a quick arterial coupler (QAC) (QAC group), and the femoral artery on the other side was anastomosed by the same person using an end-to-end suture technique with a 6-0 Prolene suture (suture group). The bilateral femoral arteries of 5 beagles were used for coupler-assisted anastomosis and hand-sewn anastomosis in vivo, respectively. Success rate, blood loss, anastomotic time, clamp time, total operation time, and patency rate were recorded. The patency of anastomosed arteries was assessed using vascular Doppler ultrasound, electromagnetic flowmeter, and pathological examination (6 weeks after surgery). RESULTS: As a novel arterial coupler, QAC was successfully designed and manufactured by using poly lactic-co-glycolic acid raw materials and 3-dimensions printing technology. Its rationality was preliminarily tested through finite element analysis and related mechanical analysis methods. The isolated arteries were successfully anastomosed with the assistance of QAC in vitro testing, which showed good anti-traction properties. In animal studies, QAC-assisted arterial anastomosis has superior profiles compared to hand-sewn anastomosis in anastomotic time (7.80 ± 1.41 vs. 16.38 ± 1.04 min), clamp time (8.80 ± 1.41 vs. 14.14 ± 1.57 min), and total operation time (46.64 ± 2.38 vs. 51.96 ± 3.65 min). The results of electromagnetic flowmeter, vascular Doppler ultrasound, and pathological examination showed that QAC-assisted anastomotic arteries were superior to hand-sewn arteries in terms of postoperative blood flow (16.86 ± 3.93 vs. 10.36 ± 0.92 mL/min) and vascular patency in 6 weeks after surgery. CONCLUSION: QAC is a well-designed and easily maneuverable device specialized for end-to-end arterial anastomosis. Application of this device may decrease thermal ischemia time and improve the patency of anastomotic arteries, thus, improving outcomes.

Morbid obesity impacts mortality among inpatients with type a aortic dissection: an analysis of the national inpatient sample.

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.