Risk factors of perivalvular leakage after transcatheter aortic valve replacement with Venus-A valve / 中华心血管病杂志

Objective: To investigate the risk factors of moderate or severe perivalvular leakage (PVL) after transcatheter aortic valve replacement (TAVR) with Veneus-A valve. Methods: This study was a single-center case-control study. The clinical data of patients with severe aortic stenosis, who underwent TAVR in the Department of Cardiology of Second Affiliated Hospital of Army Medical University from October 2017 to January 2021, were analyzed. According to the circumferential extent of prosthetic valve paravalvular regurgitation measured by transthoracic echocardiography before discharge (patients who died in hospital were referred to transesophageal echocardiography results after valve implanted), the patients were divided into moderate or severe PVL group and mild or non-PVL group. The clinical features, CT scan and analysis results of aortic root were compared between the two groups. Multivariate logistic regression analysis was used to identify the independent risk factors of postoperative moderate or severe PVL, and receiver operating characteristic (ROC) curve was used to explore the predictive value of related factors. Results: Eighty-two patients (mean age: (70.9±6.5) years, 46 males) were included in the analysis, there were 16 patients in the moderate or severe PVL group and 66 patients in the mild or non-PVL group. The proportion of male gender, depth of valve implantation, size of valve annulus and left ventricular outflow tract (LVOT), and coverage index of LVOT were significantly higher in moderate or severe PVL group than those in mild or non-PVL group (Pall<0.05). As there was a strong collinearity among the valve annular short diameter, LVOT short diameter and LVOT coverage index (partial correlation coefficient R 0.251-0.779, P<0.05), these parameters were not entered in regression model. Multivariate logistic regression analysis showed that valve implantation depth(OR=1.239,95%CI 1.036-1.442,P=0.023), aortic angulation(OR=1.128, 95%CI 1.044-1.312,P=0.038)and LVOT tract coverage index (OR=1.123, 95%CI1.003-1.315, P=0.032) were independent risk factors for moderate or severe PVL after TAVR. The ROC curve showed that the valve implantation depth could predict the occurrence of moderate or severe PVL after TAVR (area under ROC curve (AUC)=0.697, 95%CI 0.554-0.851, P=0.039). Conclusion: Among patients with severe aortic stenosis who undergo TAVR with Venus-A valve, the implantation depth, aortic angulation and LVOT coverage index are independent risk factors of moderate/severe PVL after TAVR, among which valve implantation depth could be used to predict the occurrence of moderate/severe PVL after TAVR.

Effects of inhibition of KLF4 expression by miR-29a on transformation of phenotype of vascular smooth muscle cells / 解放军医学杂志

Objective To explore whether miR-29a can influence the phenotypic transformation of vascular smooth muscle cells (VSMCs) by inhibiting expression of Kruppel-like factor 4 (KLF4). Methods Rat VSMCs were cultured primarily. The luciferase reporter system was used to verify whether KLF4 is the target gene of miR-29a. VSMCs were divided into miR-29a-transfected expression plasmid group, transfection-negative expression plasmid group, and no-transfection group. The expression of KLF4 and VSMC contractile phenotype protein levels were determined by Western blotting. The proliferation of VSMCs was analyzed by3H thymidine-incorporation assay. Results The lucierase activity was significantly decreased in wild-type KLF4 luciferase report gene and miR-29a expression plasmid co-transfection group. The KLF4 protein expression level (0.36 ± 0.02) was significantly lower in miR-29a-transfected expression plasmid group than that in untransfected and transfection-negative expression plasmid group (1.52 ± 0.06, 1.55 ± 0.05, respectively, P<0.01). Meanwhile, compared with untransfected and transfection-negative expression plasmid groups, the contractile phenotype associated protein SM-MHC, SM-22α, calponin expression levels were increased, while the proliferation capability was decreased in miR-29a-transfected expression plasmid group. Conclusion MiR-29a targets KLF4 and inhibits its expression, thus maintains contractile phenotype of VSMCs, and reduces the cell proliferation ability.

Impact of stromal interaction molecule 1 silencing on cell cycle of endothelial progenitor cells / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effect of stromal interaction molecule 1 (STIM1) silencing on EPCs cell cycle.</p><p><b>METHODS</b>Rat bone marrow derived endothelial progenitor cells (EPCs) were isolated and cultured in L-DMEM with 20% FBS. Ad-si/rSTIM1 and Ad-hSTIM1 were then transfected into EPCs and the expression of STIM1 mRNA was detected by RT-PCR. The cell cycle was determined using flow cytometry analysis and intracellular free Ca2+ was measured using LSCM. Co-immunoprecipitation was performed to examine the interaction between STIM1 and TRPC1. Protein levels of inositol 1, 4, 5-trisphosphate were analyzed with ELISA assay.</p><p><b>RESULTS</b>Forty-eight hours after transfection, the expression of STIM1 mRNA was significantly downregulated (0.37 +/- 0.02 vs. 1.00 +/- 0.02, P < 0.05) and intracellular free Ca2+ level was significantly reduced (34.07 +/- 4.10 vs. 86.51 +/- 14.12, P < 0.05) in Ad-si/rSTIM1 group compared with control group. The cell cycle was arrested at G1 phase [(90.91 +/- 1.10)% vs. (77.10 +/- 0.56)%, P < 0.05] and the store-operated channel entry was strikingly inhibited in EPCs after treatment with Ad-si/rSTIM1. However, cotransfection of Ad-hSTIM1 with Ad-si/rSTIM1 significantly reversed these responses. Interestingly, co-immunoprecipitation study showed that STIM1 co-precipitated with TRPC1, and IP3 levels measured by ELISA were similar among three groups (P > 0.05).</p><p><b>CONCLUSION</b>siRNA-mediated knockdown of STIM1 inhibited EPCs proliferation by reducing intracellular free Ca2+ through TRPC1-SOC signaling pathway.</p>

Association among circulating endothelial progenitor cells, insulin resistance and severity of coronary lesions in patients with coronary artery disease / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the correlation between the number and activity of circulating endothelial progenitor cells (EPCs), insulin resistance and severity of coronary lesions in patients with coronary artery disease (CAD).</p><p><b>METHODS</b>Patients with coronary angiography evidenced CAD were divided in insulin resistance group (IR, n = 25) and insulin sensitive group (IS, n = 44) according to insulin level, 25 health volunteers served as control. Circulating EPCs were marked as KDR/CD133+ cells via fluorescence-activated cell sorter analysis. EPCs were also isolated from peripheral blood and cultured in vitro for 7 days, identified by DiI-acLDL uptake and lectin staining methods. EPCs migration activities were determined by modified Boyden chamber assay, EPCs proliferation activities were determined by MTT assay.</p><p><b>RESULT</b>Circulating EPCs number was significantly lower in IR group compared with IS group [(0.34 +/- 0.08) per thousand vs. (0.47 +/- 0.09) per thousand, P < 0.01] and control group (P < 0.05). Both insulin resistance index (r = -0.291, P = 0.01)and Gensini score (r = -0.3984, P = 0.006)were negatively correlated with number of circulating EPCs. Proliferation and migration capacities of EPCs were also significantly lower in IR group compared to those in IS group (all P < 0.05) and control group (all P < 0.05).</p><p><b>CONCLUSIONS</b>Insulin resistance/hyperinsulinemia could aggravate severity of coronary artery lesions via reducing the number and activities of circulating EPCs in patients with CAD.</p>