Connexin 43 participates in atrial electrical remodelling through colocalization with calcium channels in atrial myocytes.

Atrial fibrillation (AF) is associated with atrial conduction disturbances caused by electrical and/or structural remodelling. In the present study, we hypothesized that connexin might interact with the calcium channel through forming a protein complex and, then, participates in the pathogenesis of AF. Western blot and whole-cell patch clamp showed that protein levels of Cav1.2 and connexin 43 (Cx43) and basal ICa,L were decreased in AF subjects compared to sinus rhythm (SR) controls. In cultured atrium-derived myocytes (HL-1 cells), knocking-down of Cx43 or incubation with 30 mmol/L glycyrrhetinic acid significantly inhibited protein levels of Cav1.2 and Cav3.1 and the current density of ICa,L and ICa,T . Incubation with nifedipine or mibefradil decreased the protein level of Cx43 in HL-1 cells. Moreover, Cx43 was colocalized with Cav1.2 and Cav3.1 in atrial myocytes. Therefore, Cx43 might regulate the ICa,L and ICa,T through colocalization with calcium channel subunits in atrial myocytes, representing a potential pathogenic mechanism in AF.

Safety and efficacy of concomitant ablation for atrial fibrillation in rheumatic mitral valve surgery: A meta-analysis.

OBJECTIVES: This review aimed to evaluate the safety and efficacy of concomitant surgical ablation (SA) for patients with atrial fibrillation (AF) undergoing rheumatic mitral valve (MV) surgery. METHODS: A systematic search of relevant studies focusing on SA for patients with AF undergoing rheumatic MV surgery was performed. The primary outcomes included mortality, efficacy, and complications. RESULTS: Four randomized controlled trials (RCTs) and four observational studies covering 1931 patients met the inclusion criteria. In RCTs, no significant differences in reoperation for bleeding, low cardiac output syndrome, thromboembolic events, and early (risk ratio [RR], 2.07; 95% confidence intervals [CI], 0.37-11.40; p = .41) and midterm all-cause death (RR, 1.07; 95% CI, 0.40-2.88; p = .89) were noted between the SA group and the nonablation group. These results were similar to those obtained from observational studies. However, ablation was associated with a higher incidence of permanent pacemaker implantation (RR, 2.44; 95% CI, 1.15-5.18; p = .02) in observational studies but not in RCTs (RR, 2.03; 95% CI, 0.19-21.26; p = .56). Furthermore, additional SA was significantly more effective in sinus rhythm (SR) restoration than MV surgery alone at discharge and at the 12-month and 3-year follow-ups. CONCLUSIONS: Concomitant SA during rheumatic MV surgery does not increase perioperative adverse events. In addition, SA promotes considerable restoration of SR. Although some evidence exists that permanent pacemaker implantation is more common after ablation, not all studies support this notion.

Activation of PKCα participates in the reduction of Ikur in atrial myocytes induced by tumour necrosis factor-α.

The atrial-specific ultra-rapid delayed rectifier K+ current (Ikur) plays an important role in the progression of atrial fibrillation (AF). Because inflammation is known to lead to the onset of AF, we aimed to investigate whether tumour necrosis factor-α (TNF-α) played a role in regulating Ikur and the potential signalling pathways involved. Whole-cell patch-clamp and biochemical assays were used to study the regulation and expression of Ikur in myocytes and in tissues from left atrial appendages (LAAs) obtained from patients with sinus rhythm (SR) or AF, as well as in rat cardiomyocytes (H9c2 cells) and mouse atrial myocytes (HL-1 cells). Ikur current density was markedly reduced in atrial myocytes from AF patients compared with SR controls. Reduction of Kv1.5 protein levels was accompanied by increased expression of TNF-α and protein kinase C (PKC)α activation in AF patients. Treatment with TNF-α dose-dependently reduced Ikur and protein expression of Kv1.5 but not Kv3.1b in H9c2 cells and HL-1 cells. TNF-α also increased activity of PKCα. Specific PKCα inhibitor Gö6976 alleviated the reduction in Ikur induced by TNF-α, but not the reduction in Kv1.5 protein. TNF-α was involved in the electrical remodelling associated with AF, probably by depressing Ikur in atrial myocytes via activation of PKCα.

High hydrostatic pressure induces atrial electrical remodeling through angiotensin upregulation mediating FAK/Src pathway activation.

Hypertension is an independent risk factor for atrial fibrillation (AF), although its specific mechanisms remain unclear. Previous research has been focused on cyclic stretch, ignoring the role of high hydrostatic pressure. The present study aimed to explore the effect of high hydrostatic pressure stimulation on electrical remodeling in atrial myocytes and its potential signaling pathways. Experiments were performed on left atrial appendages from patients with chronic AF or sinus rhythm, spontaneously hypertensive rats (SHRs) treated with or without valsartan (10 mg/kg/day) and HL-1 cells were exposed to high hydrostatic pressure using a self-developed device. Whole-cell patch-clamp recordings and western blots demonstrated that the amplitudes of ICa,L, Ito, and IKur were reduced in AF patients with corresponding changes in protein expression. Angiotensin protein levels increased and Ang1-7 decreased, while focal adhesion kinase (FAK) and Src kinase were enhanced in atrial tissue from AF patients and SHRs. After rapid atrial pacing, AF inducibility in SHR was significantly higher, accompanied by a decrease in ICa,L, upregulation of Ito and IKur, and a shortened action potential duration. Angiotensin upregulation and FAK/Src activation in SHR were inhibited by angiotensin type 1 receptor inhibitor valsartan, thus, preventing electrical remodeling and reducing AF susceptibility. These results were verified in HL-1 cells treated with high hydrostatic pressure, and demonstrated that electrical remodeling regulated by the FAK-Src pathway could be modulated by valsartan. The present study indicated that high hydrostatic pressure stimulation increases AF susceptibility by activating the renin-angiotensin system and FAK-Src pathway in atrial myocytes.

Modified unicaval drainage in reoperative isolated tricuspid valve repair via totally thoracoscopic approach.

AIM: The aim of this study was to investigate the feasibility, safety, and clinical effect of modified unicaval drainage for thoracoscopic reoperative isolated tricuspid valve repair, compared with conventional bicaval drainage. METHODS: A total of 45 consecutive cases of patients who underwent thoracoscopic reoperative isolated tricuspid valve repair on beating-heart were enrolled and divided into two groups according to the different venous drainage (Group A: modified unicaval drainage, Group B: conventional bicaval drainage). A retrospective analysis of perioperative data and clinical outcomes were performed and all the surviving cases were followed up. Re-evaluation of echocardiography and electrocardiogram was performed prior to discharge, and at first month, sixth month, and every year follow-up. RESULTS: The overall postoperative 30-day mortality was 4.5% in Group A and 8.7% in Group B. The postoperative tricuspid valve regurgitation grade of both groups decreased significantly from preoperative regurgitation grade, p < 0.001, without intergroup significant difference, p = 0.815. Follow-up duration ranged from 6 to 38 months, there was one death at 24 months in Group A, and another at 9 months in Group B, respectively. Nobody from both groups experienced reintervention for residual tricuspid regurgitation. No significant difference could be identified about the incidence of postoperative morbidities and follow-up adverse events. CONCLUSION: Both strategies of caval venous drainage can provide satisfactory exposure for thoracoscopic reoperative isolated tricuspid valve repair and equivalent favorable postoperative outcome. And the modified unicaval drainage group may even preserve the anesthetic time and decrease the risk of iatrogenic jugular injury, achieving a more simplified procedure with better cosmetic outcome.

Intraoperative Implantation of Temporary Endocardial Pacing Catheter During Thoracoscopic Redo Tricuspid Surgery.

BACKGROUND: The placement of a temporary epicardial pacing wire is a challenge during a minimally invasive redo cardiac operation. The aim of this study is to assess the application of temporary endocardial pacing in patients who underwent minimally invasive redo tricuspid surgery. METHODS: Perioperative data of consecutive patients who underwent thoracoscopic redo tricuspid surgery were collected. All the tricuspid surgeries and combined procedures were performed under peripheral cardiopulmonary bypass without aortic cross-clamping. A sheath was introduced into the right jugular vein beside the percutaneous superior vena cava cannula and a temporary endocardial pacing catheter was guided into the right ventricle via the sheath prior to the right atrial closure. The pacemaker was connected and run as needed during or after operation. RESULTS: A total of 33 patients who underwent thoracoscopic redo tricuspid surgery were enrolled. Symptomatic tricuspid valve regurgitation (93.9%) and tricuspid valvular prosthesis obstruction (6.1%) after previous cardiac operations were noted as indications for a redo surgery. The mean time from previous cardiac operation to this time redo surgery was 13.3±6.4years. Isolated tricuspid valve replacement was performed in 18 patients (54.5%) and tricuspid valve plasty combined with or without mitral valve replacement was performed in 15 patients (45.5%). A temporary endocardial pacing catheter was successfully placed in the right ventricle for all patients with good sensing and pacing. No temporary pacing related complications occurred from insertion to removal of pacing catheter in the patients. CONCLUSIONS: This application of temporary endocardial pacing provided a safe and effective substitute for epicardial pacing in patients who underwent minimally invasive redo tricuspid surgery.

Characteristics, Mechanism and Long-Term Ablation Outcome of Atrial Tachycardias After Mitral Valvular Surgery and Concomitant Cox-MAZE IV Procedure.

The incidence of atrial tachycardia (AT) after rheumatic mitral valvular (RMV) surgery has been well described. However, there have been few reports on the characteristics, mechanism, and long-term ablation outcome of ATs after RMV surgery and concomitant Cox-MAZE IV procedure.The present study reviewed consecutive patients who underwent AT ablation between May 2008 and July 2013. All patients were refractory to antiarrhythmic drugs (AADs) and had a history of RMV surgery and Cox-MAZE IV procedure. A total of 34 patients underwent AT ablation after RMV surgery and concomitant Cox-MAZE IV procedure, and presented 57 mappable and 2 unmappable ATs. The 57 mappable ATs included 14 focal-ATs and 43 reentry-ATs. Ten of the 14 focal-like ATs were located at the pulmonary vein (PV) antrum and border of a box lesion. Of the 43 reentry-ATs, 16 were marco-reentrant around the mitral annulus (MA) and 16 around the tricuspid annulus. There were 41 atypical ATs (non-cavotricuspid isthmus related) including 16 ATs related to the box lesion and 21 ATs related to other Cox-MAZE IV lesions. The AT were successfully terminated in 33 (97.1%) patients. After mean follow-up of 46.9 ± 15.7 months, 25 (73.5%) patients maintained sinus rhythm without AADs after a single procedure and 28 (82.4%) patients after repeated procedures.The recurrent ATs after RMV surgery and concomitant Cox-MAZE IV were mainly reentry mechanism, and largely related to LA. An incomplete lesion or re-conductive gaps in a prior lesion might be the predominant mechanisms for these ATs. Catheter-based mapping and ablation of these ATs seems to be effective and safe during a long-term follow-up.

Bilateral subclavian vein sheaths for superior vena cava drainage during thoracoscopic repair of atrial septal defects: cosmetic outcomes, safety and effectiveness.

OBJECTIVE: To investigate the cosmetic outcomes, safety and effectiveness of using bilateral subclavian vein sheaths for superior vena cava drainage during thoracoscopic repair of atrial septal defects. METHODS: Sixty-one consecutive adults scheduled for thoracoscopic repair of atrial septal defects between July 2012 and June 2013 were randomized into two groups: one group underwent placement of a 16 Fr percutaneous superior vena cava cannula (n = 30) and the other group underwent placement of bilateral 8 Fr subclavian vein sheaths (n = 31) for superior vena cava drainage during peripheral cardiopulmonary bypass. The perioperative data, central venous pressure during cardiopulmonary bypass, complications and the patient satisfaction scale scores for the incisions were compared between the two groups. RESULTS: The theoretical cardiopulmonary bypass flow rate was reached without complications in all patients. The average central venous pressure during cardiopulmonary bypass was not significantly different between the two groups [(6.9 ± 3.1) mmHg vs. (7.0 ± 3.5) mmHg, p=0.92]. The patient satisfaction scale scores for the incisions were significantly higher in the patients who underwent placement of bilateral subclavian vein sheaths than in the patients who underwent placement of a percutaneous superior vena cava cannula [(2.81 ± 0.75) vs. (2.07 ± 0.74), p<0.001]. CONCLUSIONS: Placement of bilateral subclavian vein sheaths is a safe and effective alternative to placement of a percutaneous superior vena cava cannula for superior vena cava drainage during thoracoscopic repair of atrial septal defects and results in greater patient satisfaction with the cosmetic outcome.

Superior vena cava drainage during thoracoscopic cardiac surgery: bilateral internal jugular vein sheaths versus one percutaneous superior vena cava cannula.

OBJECTIVE: To evaluate bilateral internal jugular vein sheaths as a replacement of one percutaneous superior vena cava cannula for superior vena cava drainage during thoracoscopic cardiac surgery. DESIGN: A prospective and randomized study. SETTING: Single cardiovascular institute. PARTICIPANTS: Adults undergoing thoracoscopic cardiac surgery. INTERVENTIONS: Patients were randomized into a percutaneous superior vena cava cannula group and a bilateral internal jugular vein sheaths group. The superior vena cava drainage for cardiopulmonary bypass was performed with one percutaneous superior vena cava cannula (14-18 Fr) or the bilateral internal jugular vein sheaths (8 Fr). MEASUREMENTS AND MAIN RESULTS: Both interventions reached theoretic flow rate in all patients. In patients weighing<50 kg (n=38) and 50-70 kg (n=64), the average central venous pressure values during cardiopulmonary bypass of both groups showed no significant differences. The patients weighing>70 kg (n=15) in the bilateral internal jugular vein sheaths group had a normal average central venous pressure value, but it was significantly higher than that of percutaneous superior vena cava cannula group ([10.5±3.1] mmHg vs. [4.5±4.4] mmHg, p=0.013). The patient satisfaction scale scores for the cervical incisions were significantly higher in the bilateral internal jugular vein sheaths group than in the percutaneous superior vena cava cannula group ([2.6±0.9] vs. [2.1±0.8], p=0.002). CONCLUSIONS: The bilateral internal jugular vein sheaths were a feasible and effective option to replace one percutaneous superior vena cava cannula during thoracoscopic cardiac surgery, with better patient satisfaction.

Native mitral valve fungal endocarditis caused by Aspergillus fumigatus: A case report.

INTRODUCTION: Aspergillus endocarditis is a rare fungal infection associated with a poor prognosis. Most cases of Aspergillus endocarditis involve prosthetic valves, with native valve involvement being rarely reported. CASE PRESENTATION: A 53-year-old asian female patient presented with fever, chills, dyspnea, generalized fatigue, and significant weight loss one month after undergoing left lower lobectomy for a pulmonary abscess. Echocardiogram showed a large mobile vegetation with a broad base on the anterior leaflet of the mitral valve, resembling atrial myxoma. Despite negative blood cultures, circulating DNA of Aspergillus fumigatus was detected by metagenome Next Generation Sequencing, prompting the initiation of empiric antifungal therapy with voriconazole. Emergency surgery, involving thorough debridement and mitral valve replacement, was successfully performed. Indefinite fungal suppression therapy with oral voriconazole is continued to mitigate the risk of recurrence. The patient survived with no signs of Aspergillus disease recurrence for four years. CLINICAL DISCUSSION: Diagnosis of Aspergillus endocarditis requires a high index of suspicion and is often delayed due to consistently negative results from blood cultures. Non-culture-based methods, particularly metagenome Next-Generation Sequencing, play a crucial role in early diagnosis and therapeutic decision-making. Surgical debridement and valve replacement are imperative for survival in cases of Aspergillus endocarditis. Voriconazole should be considered the primary fungicidal agent for its treatment. Moreover, lifelong fungal suppression therapy is strongly recommended for all survivors to ensure long-term survival and minimize the risk of recurrence. CONCLUSION: Despite grim prognosis associated with Aspergillus endocarditis, patients can attain long-term survival through meticulous surgical debridement and lifelong antifungal therapy.

Development and validation of a circulating tumor DNA-based optimization-prediction model for short-term postoperative recurrence of endometrial cancer.

BACKGROUND: Endometrial cancer (EC) is a common gynecological malignancy that typically requires prompt surgical intervention; however, the advantage of surgical management is limited by the high postoperative recurrence rates and adverse outcomes. Previous studies have highlighted the prognostic potential of circulating tumor DNA (ctDNA) monitoring for minimal residual disease in patients with EC. AIM: To develop and validate an optimized ctDNA-based model for predicting short-term postoperative EC recurrence. METHODS: We retrospectively analyzed 294 EC patients treated surgically from 2015-2019 to devise a short-term recurrence prediction model, which was validated on 143 EC patients operated between 2020 and 2021. Prognostic factors were identified using univariate Cox, Lasso, and multivariate Cox regressions. A nomogram was created to predict the 1, 1.5, and 2-year recurrence-free survival (RFS). Model performance was assessed via receiver operating characteristic (ROC), calibration, and decision curve analyses (DCA), leading to a recurrence risk stratification system. RESULTS: Based on the regression analysis and the nomogram created, patients with postoperative ctDNA-negativity, postoperative carcinoembryonic antigen 125 (CA125) levels of < 19 U/mL, and grade G1 tumors had improved RFS after surgery. The nomogram's efficacy for recurrence prediction was confirmed through ROC analysis, calibration curves, and DCA methods, highlighting its high accuracy and clinical utility. Furthermore, using the nomogram, the patients were successfully classified into three risk subgroups. CONCLUSION: The nomogram accurately predicted RFS after EC surgery at 1, 1.5, and 2 years. This model will help clinicians personalize treatments, stratify risks, and enhance clinical outcomes for patients with EC.

The regulation of intestinal flora on host's genes may play an essential role in the development of endometrial hyperplastic processes in yang deficiency individuals.

Yang-deficiency constitution (YADC) is linked to a higher vulnerability to various diseases, such as cold coagulation and blood stasis (CCBS) syndrome and infertility. Endometrial hyperplastic processes (EHPs) are a leading cause of infertility in women and are characterized by CCBS. However, it remains unclear whether YADC is related to the development of EHPs. METHODS: We recruited 202 EHPs patients including 147 with YADC (YEH group) and 55 with non-YADC (NYEH group). Fecal samples were collected from 8 YEH patients and 3 NYEH patients and analyzed using 16S rRNA V3-V4 sequencing for gut microbiota analysis. We obtained constitution survey data and a differential gut microbiota dataset from the literature for further analysis. Bioinformatics analysis was conducted using gut microbiota-related genes from public databases. RESULTS: YADC was significantly more prevalent in EHPs than non-YADC (P < 0.001), suggesting it as a potential risk factor for EHPs occurrence (ORpopulation survey = 13.471; ORhealthy women = 5.173). The YEH group had higher levels of inflammation, estrogen, and tamoxifen-related flora compared to NYEH and healthy YADC groups. There was an interaction between inflammation, estrogen, differential flora, and EHPs-related genes, particularly the TNF gene (related to inflammation) and the EGFR gene (related to estrogen), which may play a crucial role in EHPs development. CONCLUSION: YEH individuals exhibit significant changes in their gut microbiota compared to NYEH and healthy YADC. The interaction between specific microbiota and host genes is believed to play a critical role in the progression of EHPs.

Natural antioxidant-isoliquiritigenin ameliorates contractile dysfunction of hypoxic cardiomyocytes via AMPK signaling pathway.

Isoliquiritigenin (ISL), a simple chalcone-type flavonoid, is derived from licorice compounds and is mainly present in foods, beverages, and tobacco. Reactive oxygen species (ROS) is a critical factor involved in modulating cardiac stress response signaling during ischemia and reperfusion. We hypothesize that ISL as a natural antioxidant may protect heart against ischemic injury via modulating cellular redox status and regulating cardioprotective signaling pathways. The fluorescent probe H2DCFDA was used to measure the level of intracellular ROS. The glucose uptake was determined by 2-deoxy-D-glucose-(3)H accumulation. The IonOptix System measured the contractile function of isolated cardiomyocytes. The results demonstrated that ISL treatment markedly ameliorated cardiomyocytes contractile dysfunction caused by hypoxia. ISL significantly stimulated cardioprotective signaling, AMP-activated protein kinase (AMPK), and extracellular signal-regulated kinase (ERK) signaling pathways. The ROS fluorescent probe H2DCFDA determination indicated that ISL significantly reduced cardiac ROS level during hypoxia/reoxygenation. Moreover, ISL reduced the mitochondrial potential (Δψ) of isolated mouse cardiomyocytes. Taken together, ISL as a natural antioxidant demonstrated the cardioprotection against ischemic injury that may attribute to the activation of AMPK and ERK signaling pathways and balance of cellular redox status.

[Protective effect of retrograde venous perfusion of cryogenic liquid via accessory hemiazygos vein and treated with resveratrol on spinal cord injury in swine].

OBJECTIVES: To observe the protective effect of retrograde venous perfusion of cryogenic liquid via accessory hemiazygos vein and treated with resveratrol on spinal cord injury and evaluate the expression changes of microtubule-associated protein 2 (MAP-2) after spinal cord ischemia reperfusion injury (SCII) in swine. METHODS: Eighteen swine were divided into 3 groups: group I/R (n = 6, operation group), group CL (n = 6, retrograde venous perfusion of cryogenic liquid), group CL+Res (n = 6, retrograde venous perfusion of cryogenic liquid and treated with resveratrol after ischemia). In the group I/R, the aorta was clamped for 60 minutes and then removed. In the group CL and CL+Res, 9 g/L cold (4 °C) saline solution (perfusion rate, 16.65 ml/min) was infused into the accessory hemiazygos vein during ischemia.In the group CL+Res, the swine were treated with resveratrol (10 mg/kg) after spinal cord ischemia. Arterial pressure, blood gas analysis and the spinal canal and nasopharyngeal temperature changes were monitored during the surgery. Nervous function were assessed at 6 hours, 1, 2 days, 1, 2, 4 weeks and MAP-2 expression were detected at 4 weeks after reperfusion by using Western blot analysis in spinal cord tissue. RESULTS: After operation 18 swine were all survival. Behavioral scores of all groups decreased until 1 week after reperfusion and increased as time went by. The scores of group CL and CL+Res were higher than group I/R (F = 8.612, 17.276 and 11.985, P = 0.035,0.011 and 0.023) at 6 hours, 1, 2 days, group CL+Res were higher than group CL(P = 0.021) at 1 days after surgery. After descending aortic cross clamping, the spinal canal and nasopharyngeal temperature were obviously decreased in all groups and dropped to the lowest at 60 minutes after ischemia and 20 minutes after reperfusion in group I/R and the other groups respectively(F = 23.187-55.029, P < 0.01).In group CL(0.54 ± 0.26) and CL+Res (0.66 ± 0.31), the MAP-2 expression were higher than group I/R(0.37 ± 0.18) (F = 9.381, P = 0.037) , and the level in group CL+Res was higher than in group CL (P = 0.021) . CONCLUSION: Retrograde venous perfusion of cryogenic liquid via accessory hemiazygos vein and treated with resveratrol can relieve the ischemia-induced spinal cord injury in swine.

Acetyltransferase p300 regulates atrial fibroblast senescence and age-related atrial fibrosis through p53/Smad3 axis.

Atrial fibrosis induced by aging is one of the main causes of atrial fibrillation (AF), but the potential molecular mechanism is not clear. Acetyltransferase p300 participates in the cellular senescence and fibrosis, which might be involved in the age-related atrial fibrosis. Four microarray datasets generated from atrial tissue of AF patients and sinus rhythm (SR) controls were analyzed to find the possible relationship of p300 (EP300) with senescence and fibrosis. And then, biochemical assays and in vivo electrophysiological examination were performed on older AF patients, aging mice, and senescent atrial fibroblasts. The results showed that (1) the left atrial tissues of older AF patients, aging mouse, and senescence human atrial fibroblasts had more severe atrial fibrosis and higher protein expression levels of p300, p53/acetylated p53 (ac-p53)/p21, Smad3/p-Smads, and fibrosis-related factors. (2) p300 inhibitor curcumin and p300 knockdown treated aging mouse and senescence human atrial fibroblasts reduced the senescence ratio of atrial fibroblasts, ameliorated the atrial fibrosis, and decreased the AF inducibility. In contrast, over-expression of p300 can lead to the senescence of atrial fibroblasts and atrial fibrosis. (3) p53 knockdown decreased the expression of aging and fibrosis-related proteins. (4) Co-immunoprecipitation and immunofluorescence showed that p53 forms a complex with smad3 and directly regulates the expression of smad3 in atrial fibroblasts. Our findings suggest that the mechanism of atrial fibrosis induced by aging is, at least, partially dependent on the regulation of p300, which provides new sights into the AF treatment, especially for the elderly.

Matrine inhibits disturbed flow-enhanced migration via downregulation of ERK1/2-MLCK signaling vascular smooth muscle cells.

BACKGROUND: To investigate the effects of matrine on the vascular smooth muscle cell (VSMC) migration modulated by disturbed flow and their underlying molecular mechanisms in vitro. METHODS: Isolated rat aortic VSMCs were grown to confluence on 20- × 80-mm fibronectin-coated glass cover slides, and then, denuded zones were made at the position calculated to be the oscillating flow-reattachment zone and also in the downstream laminar flow region. VSMCs were treated with different doses of matrine (0, 10, 20, 30, and 40 mg/L), or PD98059 (30 µM), ML-7 (10 µM) combined with matrine (40 mg/L) for 30 minutes before and during the experiments. Then, the wounded monolayers were kept under static conditions or were subjected to laminar or disturbed flow for 21 hours or 10 hours. The VSMC migration was assessed by microscopic images. The extracellular signal-regulated kinase 1/2 (ERK1/2) and myosin light chain kinase (MLCK) proteins were determined by Western blot. RESULTS: Disturbed flow significantly increased phosphorylation of ERK1/2. Selective inhibition of ERK1/2 phosphorylation by inhibitor PD98059 and matrine significantly suppressed VSMC migration under disturbed flow. Disturbed flow significantly enhanced phosphorylation of MLCK, whereas both matrine and PD98059 inhibited the phosphorylation of MLCK under disturbed flow. The complete inhibition of MLCK phosphorylation using the selective MLCK inhibitor ML-7 significantly inhibited VSMC migration under disturbed flow. CONCLUSION: Matrine inhibits VSMC migration under disturbed flow, in part, by downregulation of ERK1/2-MLCK signaling pathway.

Suppression of the Inhibitory Effect of circ_0036176-Translated Myo9a-208 on Cardiac Fibroblast Proliferation by miR-218-5p.

Increasing evidence has shown that circular RNAs (circRNAs) participate in the process of cardiac remodeling. CircRNA circ_0036176 originating from the back-splicing of exon 2 to exon4 of myosin IXA (Myo9a) gene was shown to be increased in the myocardium of patients with heart failure (HF) and riched in exosomes from human AC16 cardiomyocytes with overexpression of circ_0036176. Proliferation activity was inhibited in mCFs subjected to exosomal circ_0036176 treatment and in mCFs with overexpression of circ_0036176. Interestingly, circ_0036176 contains an IRES element and an ORF of 627 nt encoding a 208-amino acid protein (termed as Myo9a-208). Myo9a-208 was shown to mediate the inhibitory effect of circ_0036176 on CFs proliferation, and miR-218-5p could inhibit Myo9a-208 expression by binding to circ_0036176, resulting in abolishing the effect of circ_0036176 on inactivating cyclin/Rb signal and suppressing CFs proliferation. Our findings suggest that circ_0036176 inhibits mCFs proliferation by translating Myo9a-208 protein to suppress cyclin/Rb pathway.

Clinical Characteristics and Long-Term Prognosis of Elderly Valvular Heart Disease Patients with Diabetes Mellitus: Five-Year Experience from a Single-Center Study of Southern China.

BACKGROUND: Diabetes mellitus (DM) is a prognostic marker in elderly patients with cardiovascular diseases, but its predictive value in elderly valvular heart disease (VHD) patients is unclear. This study aimed to investigate the effect of DM on the long-term outcome of elderly VHD patients. METHODS: This single-center, observational study enrolled patients aged 65 and older consecutively with confirmed VHD using echocardiography. Patients, divided into the DM group and non-DM group, were followed up for major adverse cardiac and cerebrovascular events (MACCEs), including all-cause death, ischemic stroke, and heart failure rehospitalization. RESULTS: Our study consisted of 532 patients over a median follow-up of 52.9 months. Compared with the non-DM group (n = 377), the DM group (n = 155) had higher incidences of ischemic stroke (25.2% vs. 13.5%, P=0.001), heart failure rehospitalization (37.4% vs. 20.7%, P < 0.001), and MACCEs (60.0% vs. 35.8%, P < 0.001). After adjustment of confounders by the multivariable cox regression, DM appeared as an independent predictor for MACCEs (adjusted hazard ratio, aHR: 1.88; 95% confidence interval 1.42-2.48; P < 0.001). In the subgroup analysis of VHD etiology and functional style, conversely, DM was a protective factor for MACCEs in the patients with rheumatic VHD compared with those without rheumatic VHD (aHR: 0.43 vs. 2.27, P=0.004). CONCLUSIONS: DM was an independent predictor for ischemic stroke and heart failure rehospitalization in elderly VHD patients undergoing conservative treatment.

High hydrostatic pressure induces atrial electrical remodeling through upregulation of inflammatory cytokines.

AIMS: Hypertension is an independent risk factor for atrial fibrillation (AF). However, the direct effect of hydrostatic pressure on atrial electrical remodeling is unclear. The present study investigated whether hydrostatic pressure is responsible for atrial electrical remodeling and addressed a potential role of inflammation in this pathology. MAIN METHODS: Whole-cell patch-clamp recordings and biochemical assays were used to study the regulation and expression of ion channels in left atrial appendages in patients with AF, spontaneously hypertensive rats (SHRs), and atrium-derived cells (HL-1 cells) exposed to standard (0 mmHg) and elevated (20, 40 mmHg) hydrostatic pressure. KEY FINDINGS: Both TNF-α and MIF were highly expressed in patients with AF and SHRs. AF inducibility in SHRs was higher after atrial burst pacing, accompanied by a decrease in the L-type calcium current (ICa,L), an increase in the transient outward K+ current (Ito) and ultra-rapid delayed rectifier K+ current (IKur), and a shortened action potential duration (APD), which could be inhibited by atorvastatin. Furthermore, exposure to elevated pressure was associated with electrical remodeling of the HL-1 cells. The peak current density of ICa,L was reduced, while Ito and IKur were increased. Moreover, the expression levels of Kv4.3, Kv1.5, TNF-α, and MIF were upregulated, while the expression of Cav1.2 was downregulated in HL-1 cells after treatment with high hydrostatic pressure (40 mmHg). Atorvastatin alleviated the electrical remodeling and increased inflammatory markers in HL-1 cells induced by high hydrostatic pressure. SIGNIFICANCE: Elevated hydrostatic pressure led to atrial electrical remodeling and increased AF susceptibility by upregulating inflammation.

A comparative study of three-dimensional high-definition and two-dimensional high-definition video systems in totally endoscopic mitral valve replacement.

BACKGROUND: Three-dimensional vision with improved depth perception and spatial orientation has already proved its superiority to the two-dimensional vision in endoscopic surgery. However, those benefits remain unidentified in cardiac surgery. For the first time, we compare performance of a three-dimensional high-definition video system with a two-dimensional high-definition video system in patients undergoing totally endoscopic mitral valve replacement. METHODS: We enrolled 90 patients with mitral valve disease in a single institution, from June 2013 to June 2016. Totally endoscopic mitral valve replacement was performed by the same surgeon using either a three-dimensional high-definition (n=43) or a two-dimensional high-definition (n=47) video system with the same surgical technique. Short-term outcomes were compared between the two groups. All medical records were retrieved from a prospectively maintained database of minimally invasive cardiac surgery. RESULTS: All surgeries were successfully completed under totally endoscopic guidance. There were no intraoperative complications in either group. The use of three-dimensional video system reduced aortic cross-clamp time by approximately 10% (3D vs. 2D: 65.74±14.32 vs. 72.67±14.67 min, P=0.027). No significant differences were observed in cardiopulmonary bypass time, postoperative ventilation duration, length of surgical intensive care unit stay, length of hospital stay, and major complications between the two groups. There were no perioperative deaths in either group. CONCLUSIONS: Compared with the two-dimensional video system, the three-dimensional high-definition video system provided a better surgical experience with the same operative safety for totally endoscopic mitral valve replacement.