Introduction: Mesenchymal stem cells (MSCs) transplantation has been demonstrated to be an effective strategy for the treatment of cardiovascular disease. However, the low survival rate of MSCs at local diseased tissue reduces the therapeutic efficacy. We therefore investigated the influence of MicroRNA-378 (miR-378) transfection on MSCs survival and vascularization under hypoxic-ischemic condition in vitro. Methods: MSCs were isolated from bone marrow of Sprague–Dawley rats and cultured in vitro. The third passage of MSCs were divided into the miR-378 group and control group. For the miR-378 group, cells were transfected with miR-378 mimic. Both groups experienced exposure to hypoxia (1% O₂) and serum deprivation for 24 hours, using normoxia (20% O₂) as a negative control during the process. After 24 hours of reoxygenation (20% O₂), cell proliferation and apoptosis were evaluated. Expressions of apoptosis and angiogenesis related genes were detected. Both groups were further co-cultured with human umbilical vein endothelial cells to promote vascular differentiation for another 6 hours. Vascular density was assessed thereafter. Results: Compared with the control group, MSCs transfected with miR-378 showed more rapid growth. Their proliferation rates were much higher at 72 h and 96 h under hypoxic condition (257.33% versus 246.67%, P <0.01; 406.84% versus 365.39%, P <0.05). Cell apoptosis percentage in the miR-378 group was significantly declined under normoxic and hypoxic condition (0.30 ± 0.10% versus 0.50 ± 0.10%, P <0.05; 0.60 ± 0.40% versus 1.70 ± 0.20%, P <0.01). The miR-378 group formed a larger number of vascular branches on matrigel. BCL2 level was decreased accompanied with an upregulated expression of BAX in the two experimental groups under the hypoxic environment. BAX expression was reduced in the miR-378 group under the hypoxic environment. In the miR-378 group, there was a decreased expression of tumor necrosis factor-α on protein level and a reduction of TUSC-2 under normoxic environment. Their expressions were both downregulated under hypoxic environment. For the angiogenesis related genes, enhanced expressions of vascular endothelial growth factorα, platelet derived growth factor-β and transforming growth factor-β1 could be detected both in normoxic and hypoxic-ischemic conditions. Conclusion: MiR-378 transfection could effectively promote MSCs survival and vascularization under hypoxic-ischemic condition in vitro.

Mesenchymal stem cells (MSCs) have limited potential of cardiogenic differentiation. In this study, we investigated the influence of long noncoding RNA Braveheart (lncRNA-Bvht) on cardiogenic differentiation of MSCs in vitro. MSCs were obtained from C57BL/6 mice and cultured in vitro. Cells were divided into three groups: blank control, null vector control, and lncRNA-Bvht. All three groups experienced exposure to hypoxia (1% O2) and serum deprivation for 24 h, and 24 h of reoxygenation (20% O2). Cardiogenic differentiation was induced using 5-AZA for another 24 h. Normoxia (20% O2) was applied as a negative control during the whole process. Cardiogenic differentiation was assessed, and expressions of cardiac-specific transcription factors and epithelial-mesenchymal transition (EMT)-associated biomarkers were detected. Anti-mesoderm posterior1 (Mesp1) siRNA was transfected in order to block its expression, and relevant downstream molecules were examined. Compared with the blank control and null vector control groups, the lncRNA-Bvht group presented a higher percentage of differentiated cells of the cardiogenic phenotype in vitro both under the normal condition and after hypoxia/re-oxygenation. There was an increased level of cTnT and α-SA, and cardiac-specific transcription factors including Nkx2.5, Gata4, Gata6, and Isl-1 were significantly upregulated (P < 0.01). Expressions of EMT-associated genes including Snail, Twist and N-cadherin were much higher (P < 0.01). Mesp1 exhibited a distinct augmentation following lncRNA-Bvht transfection. Expressions of relevant cardiac-specific transcription factors and EMT-associated genes all presented a converse alteration in the condition of Mesp1 inhibition prior to lncRNA-Bvht transfection. lncRNA-Bvht could efficiently promote MSCs transdifferentation into cells with the cardiogenic phenotype in vitro. It might function via enhancing the expressions of cardiac-specific transcription factors and EMT-associated genes. Mesp1 could be a pivotal intermediary in the procedure.

Background: Although atrial high-rate episode (AHRE) and atrial fibrillation (AF) cannot entirely be identical, recent studies suggest AHRE is linked to AF development and shares some characteristics with AF regarding thromboembolism. At present, there is still lack of predictive indicators for AHRE and diagnostic methods and clinical indicators for AHRE in patients without cardiac implantable electronic device (CIED). The aim of this study was thus to explore the relationship between AHRE and left atrial (LA) strain parameters with the goal of identifying high-risk populations of AHRE by LA strain characteristics. Methods: From February 2022 to May 2023, a total of 105 CIED patients were enrolled and divided into two groups based on whether AHRE had occurred: AHRE (−) group (n=65) and AHRE (+) group (n=40). Real-time three-dimensional echocardiography (RT-3DE) technique was used to obtain the LA time-volume curve. The collected dynamic images were analyzed on the Echopac 204 workstation to obtain the parameters of LA. The four-dimensional automatic LA quantitative analysis (4D Auto LAQ) technology was used to analyze the LA strain parameters: LA reservoir longitudinal strain (LASr), LA conduit longitudinal strain (LAScd), LA contraction longitudinal strain (LASct), LA reservoir circumferential strain (LASr-c), LA conduit circumferential strain (LAScd-c), LA contraction circumferential strain (LASct-c). Correlation analysis was carried out using Binary logistic regression analysis. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the diagnostic performance of LASct in AHRE. Results: Body surface area (BSA) [odds ratio (OR) =8.34, 95% confidence interval (CI): 1.32–72.30, P=0.037], LASct (OR =1.20, 95% CI: 1.05–1.39, P=0.013) and LA end-systolic volume (LAESV) (OR =1.02, 95% CI: 1.00–1.04, P=0.023) were the influencing factors of AHRE. Only LASct (OR =1.18, 95% CI: 1.01–1.38, P=0.041) was found to be an independent influencing factor of AHRE. This result remained significant after adjusting for age, sex, hypertension, diabetes, and stroke history. The ROC curve showed that the cut-off for predicting AHRE was LASct =−4.125% with sensitivity of 37.5% and specificity of 87.7%. Conclusions: This cross-sectional study found that decreased LASct (absolute value) is an independent risk factor for the AHRE and has diagnostic efficacy in certain degree for the occurrence of AHRE.

Background: Previous studies have indicated that despite adhering to current patient selection guidelines, there remains a 30% to 40% subset of patients who do not experience improvement in heart failure (HF) after receiving cardiac resynchronization therapy (CRT). We aim to utilize echocardiographic myocardial work parameters to serve as predictors of responsiveness to CRT in patients with heart failure and reduced ejection fraction (HFrEF). Methods: We prospectively recruited patients who underwent CRT at Sun Yat-sen Memorial Hospital from June 2019 to September 2022. Comprehensive preoperative information, clinical laboratory data, conventional echocardiographic parameters and myocardial work were collected for all participants, as well as follow-up data 6 months after CRT. Results: Twenty-five patients (67.6%) showed response to CRT treatment, while twelve patients (32.4%) had no response. Compared with the non-response group, the response group had larger region constructive work [RCW: the sum of constructive work (CW) in the 9 segments of the basal, mid, and apical segments of the anterior, lateral, and posterior walls], region wasted work [RWW: the sum of wasted work (WW) in the 6 segments of the basal and mid segments of the anterior septum, posterior septum and anterior walls], and the combination of RCW and RWW (RCW + RWW) in baseline (RCW: 9,695.68±2,955.40 vs. 5,219.50±2,207.68 mmHg%, P<0.001; RWW: 3,612.08±1,723.80 vs. 1,674.33±995.23 mmHg%, P=0.001; RCW + RWW: 13,307.76±3,857.71 vs. 6,893.83±2,592.83 mmHg%, P<0.001). Furthermore, global constructive work (GCW), global wasted work (GWW), GCW + GWW, RCW, RWW, and RCW + RWW had areas under the receiver operating characteristic curve (AUCs) of 0.870, 0.770, 0.860, 0.890, 0.870, and 0.910, respectively, for predicting CRT responsiveness. Conclusions: The global and regional myocardial work parameters are associated with CRT response in CRT candidates. Particularly regional myocardial work parameters appear to be promising parameters to improve selection for CRT of patients with HFrEF.

Objective: To evaluate subclinical cardiac dysfunction across distinct obesity phenotypes using myocardial work (MW) indices, and to investigate the moderating role of epicardial adipose tissue (EAT) on MW impairment. Methods: One hundred ninety-two participants were categorized by BMI and metabolic status into four groups: metabolically healthy normal weight (MHNW), metabolically healthy obesity (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy obesity (MUO). MW indices were measured using speckle-tracking echocardiography. EAT volume was quantified from ECG-gated CT scans. Associations were analyzed using ANCOVA and regression models. Results: Despite no significant differences in left ventricular ejection fraction (LVEF) among the groups, MUNW and MUO individuals exhibited significantly impaired MW, characterized by lower global work index (GWI), global constructive work (GCW), and global work efficiency (GWE), alongside higher global waste work (GWW), compared with MHNW controls. MHO patients showed significantly better MW profiles than MUNW and MUO groups. EAT volume was increased in all obesity phenotype groups. Although no direct association was found between EAT volume and MW indices, EAT volume significantly moderated the relationship between Metabolically Unhealthy (MUH) and both GWE and GWW. Conclusions: MW detects subclinical dysfunction earlier than LVEF across obesity phenotypes, with impairment progressively worsening from MHO to MUNW to MUO. In metabolically unhealthy individuals with increased EAT volume, more pronounced reductions in GWE and elevations in GWW were observed. Trial Rrgistration: This study has been registered in the Chinese Clinical Trial Registry under the registration number ChiCTR2500100754 (registration date: April 15, 2025).