Ischemia/reperfusion (I/R) injury is an inevitable process during heart transplant and suppressing I/R injury could greatly improve the survival rate of recipients. Mesenchymal stem cells (MSCs) have positive effects on I/R. We aimed to investigate the mechanisms underlying the protective roles of MSCs in I/R. Both cell model and rat model of myocardial I/R were used. MTT assay and flow cytometry were used to measure cell viability and apoptosis, respectively. QRT-PCR and western blotting were employed to measure levels of lncRNA HCP5 (HLA complex P5), miR-497, apoptosis-related proteins, and insulin-like growth factor (IGF1)/PI3K/AKT pathway. Dual luciferase assay was used to validate interactions of HCP5 and miR-497, miR-497 and IGF1. Echocardiography was performed to evaluate cardiac function of rats. Serum levels of CK-MB and LDH were measured. H&E and Masson staining were used to examine morphology of myocardial tissues. hBMSC-derived exosomes (hBMSC-Exos) increased the viability of cardiomyocytes following hypoxia/reperfusion (H/R) and decreased apoptosis. H/R diminished HCP5 expression in cardiomyocytes while hBMSC-Exos recovered the level. Overexpression of HCP5 in hBMSC-Exos further enhanced the protective effects in H/R while HCP5 knockdown suppressed. HCP5 directly bound miR-497 and miR-497 targeted IGF1. miR-497 mimics or si-IGF1 blocked the effects of HCP5 overexpression. Further, hBMSC-Exos alleviated I/R injury in vivo and knockdown of HCP5 in hBMSC-Exos decreased the beneficial effects. AntagomiR-497 blocked the effects of HCP5 knockdown. HCP5 from hBMSC-Exos protects cardiomyocytes against I/R injury via sponging miR-497 to disinhibit IGF1/PI3K/AKT pathway. These results shed light on mechanisms underlying the protective role of hBMSC-Exos in I/R.
20 November 2020 in Frontiers in Cardiovascular Medicine
Circular RNAs (circRNA) are involved in a variety of human heart diseases, however, circRNA expression profiles and circRNA-miRNA-mRNA regulatory network in human atrial fibrillation (AF) especially with valvular heart diseases (VHD) remain poorly understood. A high-throughput RNA sequencing was used to investigate the differentially expressed circRNAs in left atrial appendage from VHD patients with or without persistent AF. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to predict the potential functions of the host genes of differentially expressed circRNA and their downstream targets. CircRNA–miRNA-mRNA regulatory network was constructed to identify mechanisms underlying circRNAs. qRT-PCR and sanger sequencing were further performed to validate the results. Compared with sinus rhythm (SR) patients, there were 3094 upregulated and 4472 downregulated circRNAs in AF patients respectively. The expression of 10 most differentially expressed circRNAs (circ 255-ITGA7, circ 418-KCNN2, circ 13913-MIB1, circ 44670-BARD1, circ 44782-LAMA2, circ 81906-RYR2, circ 35880-ANO5, circ 22249-TNNI3K, circ 3136-TNNI3K, circ 56186-TNNI3K) between SR and persistent AF patients were verified by qRT-PCR. In addition, specific back-splicing sites of these circRNAs was confirmed by sanger sequencing. GO and KEGG pathway analysis indicated that cAMP signal pathway and Wnt signal pathway might play important role in the development of AF in VHD patients, which might be affected by circRNAs. This study provided a preliminary landscape of circRNAs expression profiles which are involved in persistent AF due to VHD, and established the possibility for future related researches in this field.
Objective: To evaluate the outcome of TEVAR for TBAD and revascularization of LSA with Castor single-branched stent-graft. Summary background data: One-stage thoracic endovascular aortic repair (TEVAR) and revascularization of left subclavian artery (LSA) of type B aortic dissection (TBAD) with off-the-shelf stent-graft is limited. Methods: A multicenter study consisting of consecutive patients from four different centers in China treated with Castor single-branched stent-graft for TBAD was conducted. Rate of technical success, mortality, complications, and reinterventions were evaluated. Results: Between September 2018 and April 2022, 180 consecutive patients with TBAD received TEVAR with Castor single-branched stent-graft. Technical success was achieved in all patients. The mean oversize ratio at the proximal landing zone was 4.9±3.8% (median, 3.7; IQR, 2.0–6.9%). Five patients died within the first 30 days after the operation or during hospitalization. Early reintervention was performed in one case. The median follow-up was 18.0 months (IQR, 13–24 months). Five patients died during follow-up, including three cases of respiratory failure, one case of immune thrombocytopenia purpura, and one case of a cerebral hemorrhage. Three patients had reintervention. In total, three cases of stroke were recorded, which were all within 30 days after the operation. Image data at 1 year presented complete thrombosis in 97.1% cases for the false lumen covered by the stent-graft. Conclusions: TEVAR with Castor device for treatment of TBAD and revascularization of LSA is a feasible and safe technique. The deployment procedure is safe, easy, and accurate. Castor devices meets the hemodynamical and biomechanical requirement of elastic aorta and could restore the physiological blood flow pattern of LSA.
Aortic dissection (AD) is a life-threatening cardiovascular disease with a dismal prognosis. Inflammation plays an important role in AD. Oxylipins are bioactive lipids involved in the modulation of inflammation and may be involved in the pathogenesis and progression of AD. This study aims to identify possible metabolites related to AD. A total of 10 type A Aortic dissection (TAAD) patients, 10 type B Aortic dissection (TBAD) patients and 10 healthy controls were included in this study. Over 100 oxylipin species were identified and quantified by liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis. Our investigation demonstrated substantial alterations in 91 oxylipins between AD and healthy individuals. Patients with TAAD had 89 entries accessible compared to healthy controls. According to orthogonal partial least squares discriminant analysis (OPLS-DA), fitness (R2X = 0.362 and R2Y = 0.807, p = 0.03) and predictability (Q2 = 0.517, p = 0.005) are the validation parameters between the two groups. Using multivariate logistic regression, 13-HOTrE and 16(17)-EpDPE were the risk factors in the aortic patients group compared to healthy people (OR = 2.467, 95%CI:1.256–7.245, p = 0.035; OR = 0.015, 95%CI:0.0002–0.3240, p = 0.016, respectively). In KEGG enrichment of differential metabolites, the arachidonic acid metabolism pathway has the most metabolites involved. We established a diagnostic model in distinguishing between AD and healthy people. The AUC was 0.905. Oxylipins were significantly altered in AD patients, suggesting oxylipin profile is expected to exploit a novel, non-invasive, objective diagnosis for AD.
21 September 2017 in Journal of Cardiothoracic Surgery
Reoperative cardiac valve surgery via sternotomy is associated with a substantial morbidity and mortality. This study evaluated the right anterolateral thoracotomy for high-risk patients undergoing mitral and tricuspid valve redo procedures. Out of a series of 173 patients undergoing redo cardiac valve surgery, 24 patients were reoperative via the right anterolateral thoracotomy as the high-risk group on the basis of the proximity of the heart and great vessels to the sternum and the presence and location of patent bypass grafts. In all cases, sternotomy was avoided. The mitral valve and tricuspid valve were replaced in 4 and 19 patients and repaired in 1 and 2 patients, respectively. Moreover, left atrial folding was performed in 5 patients. Mortality was 8.3%. All other patients had uneventful outcomes and normal valve function at follow-up. Reoperative cardiac valve surgery can be performed safely using the right anterolateral thoracotomy in high-risk patients. It offers enough exposure. It minimizes the need for cardiac dissection, and thus, the risk for injury. Avoiding a high-risk resternotomy increases patients comfort and safety of redo mitral and tricuspid valve surgery.
8 November 2024 in Frontiers in Cardiovascular Medicine
Introduction: Corrected QT interval (QTc) is a ventricular repolarization marker on electrocardiography. Previous studies evaluated its value in predicting atrial fibrillation (AF) occurrence. However, its predictive efficacy for AF recurrence remains controversial.Methods: We searched PubMed and Google databases for studies before January 2024 evaluating the association between QTc interval and AF incidence. A meta-analysis of the eligible datasets was conducted using Bazett's formula, with subgroup analysis to explore the heterogeneity. Additionally, thirty-eight patients with AF who underwent radiofrequency catheter ablation were enrolled and followed-up for 3–36 months. Univariate and multivariate Cox models were used to calculate the hazard ratios (HRs) and determine the relationship between clinical factors and AF recurrence. Kaplan-Meier survival analysis and ROC curve were conducted to assess the impact and predictive efficacy of individual factors.Results: Eleven datasets from nine eligible studies were enrolled and meta-analysed. We found that patients with prolonged QTc interval was associated with a significantly higher AF incidence risk, and the risk increased with every 10-ms prolongation. However, this association was not significant in the AF recurrence subgroup. In our prospective cohort, the preoperative body mass index, QTc, left atrial diameter (LAD), and uric acid levels influenced AF recurrence. Multivariate Cox regression analysis identified LAD as an independent factor affecting AF recurrence in patients with a high predictive efficiency. Kaplan-Meier survival analysis showed that increased LAD (>4.5 cm) was associated with postoperative AF recurrence.Discussion: Therefore, LAD has better predictive power and can be an indicator for predicting postoperative AF recurrence.