Metformin alleviates the calcification of aortic valve interstitial cells through activating the PI3K/AKT pathway in an AMPK dependent way.

BACKGROUND: Calcific aortic valve disease (CAVD) is the most prevalent valvular disease worldwide. However, no effective treatment could delay or prevent the progression of the disease due to the poor understanding of its pathological mechanism. Many studies showed that metformin exerted beneficial effects on multiple cardiovascular diseases by mediating multiple proteins such as AMPK, NF-κB, and AKT. This study aims to verify whether metformin can inhibit aortic calcification through the PI3K/AKT signaling pathway. METHODS: We first analyzed four microarray datasets to screen differentially expressed genes (DEGs) and signaling pathways related to CAVD. Then aortic valve samples were used to verify selected genes and pathways through immunohistochemistry (IHC) and western blot (WB) assays. Aortic valve interstitial cells (AVICs) were isolated from non-calcific aortic valves and then cultured with phosphate medium (PM) with or without metformin to verify whether metformin can inhibit the osteogenic differentiation and calcification of AVICs. Finally, we used inhibitors and siRNA targeting AMPK, NF-κB, and AKT to study the mechanism of metformin. RESULTS: We screened 227 DEGs; NF-κB and PI3K/AKT signaling pathways were implicated in the pathological mechanism of CAVD. IHC and WB experiments showed decreased AMPK and AKT and increased Bax in calcific aortic valves. PM treatment significantly reduced AMPK and PI3K/AKT signaling pathways, promoted Bax/Bcl2 ratio, and induced AVICs calcification. Metformin treatment ameliorated AVICs calcification and apoptosis by activating the PI3K/AKT signaling pathway. AMPK activation and NF-κB inhibition could inhibit AVICs calcification induced by PM treatment; however, AMPK and AKT inhibition reversed the protective effect of metformin. CONCLUSIONS: This study, for the first time, demonstrates that metformin can inhibit AVICs in vitro calcification by activating the PI3K/AKT signaling pathway; this suggests that metformin may provide a potential target for the treatment of CAVD. And the PI3K/AKT signaling pathway emerges as an important regulatory axis in the pathological mechanism of CAVD.

Outcomes and preoperative evaluation of transfemoral transcatheter aortic valve replacement (TAVR) in the treatment of pure native aortic valve regurgitation / 中国胸心血管外科临床杂志

@#Objective    To assess outcomes of transcatheter aortic valve replacement (TAVR) for pure native aortic valve regurgitation. Methods    A total of 129 patients underwent transfemoral TAVR in Fuwai Hospital from May 2019 to October 2020 were retrospectively analyzed. There were 83 males and 46 females with an average age of 72.26±8.97 years. The patients were divided into a pure native aortic valve regurgitation group (17 patients) and an aortic valve stenosis group (112 patients). Results    The incidence of valve in valve was higher in the pure native aortic valve regurgitation group (47.0% vs. 16.1%, P<0.01). There was no statistical difference between the two groups in conversion to surgery, intraoperative use of extracorporeal circulation, intraoperative left ventricular rupture, postoperative use of extracorporeal membrane oxygenation (ECMO), peripheral vascular complications, disabled stroke, death, or pacemaker implantation. There was no statistical difference in the diameter of annulus (25.75±2.21 mm vs. 24.70±2.90 mm, P=0.068) or diameter of outflow tract (25.82±3.75 mm vs. 25.37±3.92 mm, P=0.514) between the pure native aortic valve regurgitation group and the aortic valve stenosis group. Conclusion    Transfemoral TAVR is a feasible method for patients with pure native aortic valve regurgitation. The diameter of annulus plane, the diameter of outflow tract and the shape of outflow tract should be evaluated.

Comparison of 1-year clinical results of transcatheter aortic valve replacement (TAVR) using prostheses with two different frame designs in 124 patients in a single center / 中国胸心血管外科临床杂志

@#Objective    To compare and analyze the clinical effects of two kinds of frame design valves after transcatheter aortic valve replacement (TAVR). Methods    We retrospectively reviewed 124 patients who underwent TAVR and were followed up for 1 year. There were 71 males and 53 females aged 75.57±6.21 years. These patients were treated with Venus-A or Edwards Sapien aortic valves. The hemodynamics and cardiac function of these two kinds of transcatheter aortic valves (THV) were evaluated by echocardiography. The 30-day mortality and 1-year clinical effect of the patients were calculated. Results    Eight-one patients used Venus-A valve and 43 patients used Edwards Sapien valve. The aortic valve transaortic pressure gradient was reduced and the rate of perivalvular leakage was low (both 2.6%) in both groups, and there was no statistical difference between the two groups. The implantation rate of permanent pacemaker was 17.3% and 11.6%, respectively. The 1-month survival (94.0% and 93.0%) and 1-year survival (94.0% and 91.0%) rates were not statistically different. Conclusion    The two groups of THV with different stent structures have good short-term clinical effect and low implantation rate of permanent pacemaker.

Short-term Effect and Risk Factor Analysis on the Timing of Intra-aortic Balloon Pump Implantation for Coronary Artery Bypass Grafting in Patients With High Risk Coronary Artery Disease / 中国循环杂志

Objective: To evaluate short-term effect and risk factors for the timing of intra-aortic balloon pump (IABP) implantation with coronary artery bypass grafting (CABG) in high risk coronary artery disease (CAD) patients. Methods: A total of 197 high risk CAD patients received IABP with CABG in our hospital from 2010-01 to 2015-12 were retrospectively analyzed. There were 91 (46.2%) male and the mean arterial pressure (MAP) was (70.3±8.2) mmHg. Based on IABP implantation time, the patients were divided into 2groups: Pre-operative IABP group,n=89 and Intra- , post-operative IABP group,n=108. Peri-operative condition, durations of mechanical ventilation and ICU stay were compared between 2 groups; survival condition was studied by Kaplan-Meier analysis; risk factors causing 30-day mortality was assessed by Logistic regression analysis and its sensitivity and specialty was measured by ROC curve. Results: The mean durations for aortic clamping and cardiopulmonary bypass were (86.7±37.3) min and (147.3±18.4) min in all 197 patients. The age, gender, blood levels of CK-MB c-TnI, creatinine, MAP and European cardiac surgery system scoring were similar between 2 groups, allP>0.05. Compared with Intra- , post-operative IABP group, Pre-operative IABP group had decreased CK-MB (130.6±25.4) mmol/L vs (149.7±18.2) mmol/L at 48h post-operation and mechanical ventilation time (81.5±10.3) h vs (107.9±11.5) h, less in-hospital stay (21.3±4.1) d vs (27.7±9.4) d, reduced acute kidney injury (3.4% vs 23.1%), brain complication (5.6% vs 19.4%) and 30-day mortality (4.5% vs 36.1%), allP<0.05. Kaplan-Meier analysis indicated that the median survival time was longer in Pre-operative IABP group, (27.9±1.2 vs 16.5±2.2) dP<0.05; Logistic regression analysis and ROC curve demonstrated that IABP re-implantation (OR=2.37, 95% CI 1.42-5.72,P=0.01) was an important risk factor for 30-day mortality with the sensitivity of 75.3% and specialty of 67.4%. Conclusion: Pre-operative IABP implantation was helpful for decreasing post-operative level of CK-MB, reducing mechanical ventilation, in-hospital time and short-term mortality in high risk CAD patients; IABP re-implantation was the risk factor for short-term mortality.

Application of the descending branch of the lateral circumflex femoral artery in the coronary artery bypass grafting operation / 中华外科杂志

Objective@#To investigate the technical method for harvesting and application of the descending branch of the lateral circumflex femoral artery (DBLCFA) in the coronary artery bypass grafting (CABG) operation.@*Methods@#Between December 2016 and April 2017, 19 patients were arranged to use DBLCFA and got CT angiography (CTA) of pelvic and femoral arteries pre-operative at Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Finally, DBLCFA was harvested in 16 patients (including 2 female patients, with a mean age of (47.4±8.5) years) through the anterior thigh incision (13 cases on the left side, 3 cases on the right side). The CABG operations were performed under the cardiopulmonary bypass support (in 10 cases) or under the beating heart condition (in 6 cases), and the DBLCFA conduit was used combining with bilateral internal thoracic artery (in 12 cases), radial artery (in 7 cases) and saphenpous vein (in 3 cases).@*Results@#Due to anatomical variations such as short length and anomalous branch, or due to silent atherosclerosis stenosis of femoral artery, DBLCFA in 3 patients was considered inappropriate for use and was not harvested after CTA examination. In another 16 patients, DBLCFA was safely and quickly harvested and successfully used. On average, 3.4±0.6 anastomosis was built up in CBAG, no adverse effects were exhibited. The length of the harvested DBLCFA was (10.3±1.8) cm, with average lumen diameter of (1.9±0.5) mm. DBLCFA was used as free graft in 15 patients (7 to the first diagonal branch, 6 to the ramus intermedius branch, 1 to the left anterior descending branch and 1 to the second obtuse marginal branch). In 1 patient, the DBLCFA was firstly implanted end-to-side to the internal thoracic artery as a "Y" type composite graft, and then anastomosed to the third obtuse marginal branch.@*Conclusions@#The descending branch of the lateral circumflex femoral artery is an option conduit in CABG. It can be harvested easily and safely. However, pre-operative CTA examination is necessary to exclude the variation and appropriate strategy for graft establishment should be considered during the operation.