RESUMO
Objective: To evaluate the safety and efficacy of transcatheter aortic valve replacement (TAVR) with domestic prostheses in patients with severely stenotic bicuspid aortic valve (BAV). Methods: This study was a prospective single-center non-randomized controlled study. Patients with symptomatic severe aortic stenosis (AS), who underwent TAVR with domestic prostheses at the First Affiliated Hospital of Air Force Medical University from January 2016 to April 2020 were consecutively included in our study. Patients were divided into BAV group and tricuspid aortic valve (TAV) group according to the aortic valve morphology. Baseline characteristics, procedural outcomes were compared between the two groups, and the primary endpoint was one-month all-cause mortality. Results: A total of 100 patients aged (69.8±8.9) years were enrolled, including 71 (71%) males. There were 51 cases in BAV group and 49 cases in TAV group. Compared with TAV group, patient in the BAV group was younger ((67.1±8.6) years vs. (72.7±8.4) years, P=0.002) and had larger ascending aortic diameter at proximal part ((39.7±5.7) mm vs. (36.0±4.2) mm, P<0.001), lower Society of Thoracic Surgeons-Predicted Risk of Mortality (STS-PROM) score (3.1 (1.9, 5.4) % vs. 5.9 (2.6, 12.3) %, P=0.002). In BAV group and TAV group, the incidence of 2nd prosthesis implantation was 15.7% (8/51) and 18.4% (9/49) (P=0.721), the incidence of moderate or severe paravalvular regurgitation was 2.0% (1/51) and 0 (P=1.000), the rate of device success was 82.4% (42/51) and 81.6% (40/49) (P=0.925), respectively. One-month all-cause mortality was 2.0% (1/51) and 10.2% (5/49) (P=0.108), respectively. Echocardiography showed that postprocedural mean pressure gradient (PGmean) was higher in the BAV group (13.0 (10.0, 16.0) mmHg vs. 9.0 (7.0, 14.0) mmHg, P=0.003) (1 mmHg=0.133 kPa), but the PGmean decrease post procedure as compared with that before TAVR was similar between the two groups ((36.7±16.6) mmHg vs. (36.2±17.5) mmHg, P=0.893). Conclusion: Favorable safety and efficacy are evidenced in patients with severely stenotic BAV undergoing TAVR with domestic prostheses.
RESUMO
The adaptor molecule Disabled-2 (Dab2) has been shown to link cell surface receptors to downstream signaling pathways. Using a small-pool cDNA screening strategy, we identify that the N-terminal domain of Dab2 interacts with Dishevelled-3 (Dvl-3), a signaling mediator of the Wnt pathway. Ectopic expression of Dab2 in NIH-3T3 mouse fibroblasts attenuates canonical Wnt/beta-catenin-mediated signaling, including accumulation of beta-catenin, activation of beta-catenin/T-cell-specific factor/lymphoid enhancer-binding factor 1-dependent reporter constructs, and endogenous cyclin D1 induction. Wnt stimulation leads to a time-dependent dissociation of endogenous Dab2-Dvl-3 and Dvl-3-axin interactions in NIH-3T3 cells, while Dab2 overexpression leads to maintenance of Dab2-Dvl-3 association and subsequent loss of Dvl-3-axin interactions. In addition, we find that Dab2 can associate with axin in vitro and stabilize axin expression in vivo. Mouse embryo fibroblasts which lack Dab2 exhibit constitutive Wnt signaling as evidenced by increased levels of nuclear beta-catenin and cyclin D1 protein levels. Based on these results, we propose that Dab2 functions as a negative regulator of canonical Wnt signaling by stabilizing the beta-catenin degradation complex, which may contribute to its proposed role as a tumor suppressor.
