MicroRNAs have emerged as key regulators in vascular diseases and are involved in the formation of atherosclerotic lesions. However, the atherosclerotic-specific MicroRNAs and their functional roles ...in atherosclerosis are unclear. Here, we report that miR-378c protects against atherosclerosis by directly targeting Sterile Alpha Motif Domain Containing 1 (Samd1), a predicted transcriptional repressor. miR-378c was strikingly reduced in atherosclerotic plaques and blood of acute coronary syndrome (ACS) patients relative to healthy controls. Suppression of miR-378c promoted vascular smooth muscle cells (VSMCs) phenotypic transition during atherosclerosis. We also reported for the first time that Samd1 prolonged immobilization of LDL on the VSMCs, thus facilitated LDL oxidation and subsequently foam cell formation. Further, we found that Samd1 contains predicted DNA binding domain and directly binds to DNA regions as a transcriptional repressor. Together, we uncovered a novel mechanism whereby miR-378c-Samd1 circuit participates in two key elements of atherosclerosis, VSMCs phenotypic transition and LDL oxidation. Our results provided a better understanding of atherosclerosis pathophysiology and potential therapeutic management by targeting miR-378c-Samd1 circuit.
Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical practice and a major cause of morbidity and mortality. Although the fundamental mechanisms underlying AF remain ...incompletely understood, atrial remodeling, including structural, electrical, contractile, and autonomic remodeling, has been demonstrated to contribute to the substrate for AF maintenance. Accumulating evidence shows that tumor necrosis factor alpha (TNF-α) plays exceedingly important roles in atrial remodeling. This article reviews recent advances in the roles of TNF-α in the pathogenesis of AF, elucidates the related mechanisms, and exploits its potential usefulness as a novel therapeutic target.
Researchers have investigated ways to develop optimal imaging techniques to increase the safety and effectiveness of electrophysiological (EP) procedures. Intracardiac echocardiography (ICE) is an ...advanced imaging tool that can directly visualize cardiac anatomical structures in high resolution, assess tissue heterogeneity and arrhythmogenic substrates, locate intracardiac catheters, monitor catheter-tissue contact and ablation injury in real-time, excluding intracardiac thrombi, and quickly detect procedural complications. Additionally, real-time imaging via ICE can be integrated with a three-dimensional (3D) electroanatomical mapping (EAM) system to reconstruct cardiac anatomy. This technique also promotes the development of zero-radiation EP procedures. Many EP studies and procedures have implemented ICE because it has several advantages over fluoroscopy and transesophageal echocardiography (TEE). ICE-guided EP procedures can be performed under conscious sedation; esophageal intubation and additional anesthesiologists are not required. Atrial fibrillation (AF) and supraventricular tachycardias (SVT) are the most common tachyarrhythmias in clinical settings. A comprehensive understanding of critical anatomical structures, such as the atrial septum, fossa ovalis (FO), and great heart vessels, is needed for the successful catheter ablation of these arrhythmias.Researchers have investigated ways to develop optimal imaging techniques to increase the safety and effectiveness of electrophysiological (EP) procedures. Intracardiac echocardiography (ICE) is an advanced imaging tool that can directly visualize cardiac anatomical structures in high resolution, assess tissue heterogeneity and arrhythmogenic substrates, locate intracardiac catheters, monitor catheter-tissue contact and ablation injury in real-time, excluding intracardiac thrombi, and quickly detect procedural complications. Additionally, real-time imaging via ICE can be integrated with a three-dimensional (3D) electroanatomical mapping (EAM) system to reconstruct cardiac anatomy. This technique also promotes the development of zero-radiation EP procedures. Many EP studies and procedures have implemented ICE because it has several advantages over fluoroscopy and transesophageal echocardiography (TEE). ICE-guided EP procedures can be performed under conscious sedation; esophageal intubation and additional anesthesiologists are not required. Atrial fibrillation (AF) and supraventricular tachycardias (SVT) are the most common tachyarrhythmias in clinical settings. A comprehensive understanding of critical anatomical structures, such as the atrial septum, fossa ovalis (FO), and great heart vessels, is needed for the successful catheter ablation of these arrhythmias.
Oral anticoagulation (OAC) prevents thromboembolism yet greatly increases the risk of bleeding, inciting concern among clinicians. Current guidelines lack sufficient evidence supporting long-term OAC ...following successful atrial fibrillation catheter ablation (CA). A literature search was performed in PubMed, Google Scholar, Medline, and Scopus to seek out studies that compare continued and discontinued anticoagulation in post-ablation Atrial fibrillation (AF) patients. Funnel plots and Egger’s test examined potential bias. Via the random-effects model, summary odds ratios (OR) with 95% confidence intervals (CI) were calculated using RevMan (5.4) and STATA (17.0). Twenty studies, including 22 429 patients (13 505 off-OAC) were analyzed. Stratified CHA2DS2-VASc score ≥2 examining thromboembolic events (TE) favored OAC continuation (OR 1.86; 95% CI: 1.02-3.40; P = .04). Sensitivity analysis demonstrated this association was attenuated. The on-OAC arm had greater incidence of major bleeding (MB) (OR 0.16; 95% CI: 0.08-0.95; P < .00001), particularly intracranial hemorrhage (ICH) and gastrointestinal bleeding (GI); (OR 0.17; 95% CI: 0.08-0.36; P < .00001) and (OR 0.12; 95% CI: 0.04-0.32; P < .0001), respectively. Our findings support sustained anticoagulation in patients with a CHA2DS2-VASc score of ≥2. Due to reduced outcome robustness, physician discretion is still advised.
Myocardial infarction (MI) imposes a huge medical and economic burden on society, and cardiac repair after MI involves a complex series of processes. Understanding the key mechanisms (such as ...apoptosis, autophagy, inflammation, and fibrosis) will facilitate further drug development and patient treatment. Presently, a substantial body of evidence suggests that the regulation of epigenetic processes contributes to cardiac repair following MI, with DNA methylation being among the notable epigenetic factors involved. This article will review the research on the mechanism of DNA methylation regulation after MI to provide some insights for future research and development of related drugs.
Atherosclerosis (AS) is a chronic inflammatory disease that contributes to multiple cardiovascular diseases (CVDs), and foam cell formation plays important roles in the progression of AS. There is an ...urgent need to identify new molecular targets for treating AS, and thereby improve the quality of life and reduce the financial burden of individuals with CVD.
An in vitro model of AS was generated by treating THP-1 cells and human aortic vascular smooth muscle cells (HA-VSMCs) with oxidized low-density lipoproteins (ox-LDLs). HA-VSMC proliferation and foam cell formation were detected by the MTT assay and Oil Red O staining. C-X-C motif chemokine 12 (CXCL12) expression was suppressed by siRNA. An AS rat model was established by feeding rats a high-fat diet and vitamin D2 for 3 weeks. Histopathology examinations were conducted by Hematoxylin and Eosin (H&E) staining and the levels ionized calcium-binding adapter molecule 1 (IBA1) and α smooth muscle actin (α-SMA) expression were determined by ELISA assays and immunohistochemistry.
An in vitro model of AS was established with THP-1 cells. CXCL12 expression in the model THP-1 cells was significantly increased when compared with its expression in control cells. Suppression of CXCL12 expression reduced the progression of AS in the cell model. Moreover, CXCL12 promoted AS in the in vivo rat model.
Our results suggest that CXCL12 plays an important role in promoting the progression of AS. Furthermore, inhibition of CXCL12 might suppress the development of AS by inhibiting HA-VSMC proliferation and their transformation to foam cells.
Left ventricular thrombus (LVT) formation in patients with acute myocardial infarction (AMI) or cardiomyopathies is not uncommon. The optimal oral anticoagulation therapy for resolving LVT has been ...under intense debate. Vitamin K antagonists (VKAs) remain the anticoagulant of choice for this condition, according to practice guidelines. Evidence supporting the use of direct oral anticoagulants (DOACs) in the management of LVT continues to grow. We performed a systematic review and meta-analysis to compare the efficacy and safety of DOACs versus VKAs.
A comprehensive literature search was carried out in PubMed, Cochrane Library, Web of Science, Embase, and Scopus databases in July 2023. The efficacy outcomes of this study were thrombus resolution, ischemic stroke, systemic embolism, stroke/systemic embolism, all-cause mortality, and adverse cardiovascular events. The safety outcomes were any bleeding, major bleeding, and intracranial hemorrhage. A total of twenty-seven eligible studies were included in the meta-analysis. Data were analyzed utilizing Stata software version 15.1.
There was no significant difference between DOACs and VKAs with regard to LVT resolution (RR = 1.00, 95% CI 0.95-1.05, P = 0.99). In the overall analysis, DOACs significantly reduced the risk of stroke (RR = 0.74, 95% CI 0.57-0.96, P = 0.021), all-cause mortality (RR = 0.70, 95% CI 0.57-0.86, P = 0.001), any bleeding (RR = 0.75, 95% CI 0.61-0.92, P = 0.006) and major bleeding (RR = 0.67, 95% CI 0.52-0.85, P = 0.001) when compared to VKAs. Meanwhile, in the sub-analysis examining randomized controlled trials (RCTs), the aforementioned outcomes no longer differed significantly between the DOACs and VKAs groups. The incidences of systemic embolism (RR = 0.81, 95% CI 0.54-1.22, P = 0.32), stroke/systemic embolism (RR = 0.85, 95% CI 0.72-1.00, P = 0.056), intracranial hemorrhage (RR = 0.59, 95% CI 0.23-1.54, P = 0.28), and adverse cardiovascular events (RR = 0.99, 95% CI 0.63-1.56, P = 0.92) were comparable between the DOACs and VKAs groups. A subgroup analysis showed that patients treated with rivaroxaban had a significantly lower risk of stroke (RR = 0.24, 95% CI 0.08-0.72, P = 0.011) than those in the VKAs group.
With non-inferior efficacy and superior safety, DOACs are promising therapeutic alternatives to VKAs in the treatment of LVT. Further robust investigations are warranted to confirm our findings.
Abstract Background The increasing use of intracardiac echocardiography (ICE) in the ablation of premature ventricular complexes (PVCs) has raised questions about its true efficacy and safety. ...Methods This retrospective study collected the periprocedural complications and PVC burden post ablation. The risk factors of PVC recurrence was further explored. Results The study included patients treated without ICE (control group, n = 451) and with ICE (ICE group, n = 155) from May 2019 to July 2022. The ICE group demonstrated significantly lower fluoroscopy times and X-ray doses. There were no major complications in the ICE group, and the difference in the occurrence of periprocedural complications between the groups was not statistically significant ( p = 0.072). The long-term success rates were similar for the control and ICE groups (89.6% and 87.1%, respectively). The origin of PVCs was identified as the independent factor for ablation success. Conclusions The use of ICE did not confer an advantage with regard to long-term success in PVCs ablation. To thoroughly evaluate the safety and effectiveness of ICE in PVCs ablation, a prospective, multicenter, randomized study is warranted.
Novel oral anticoagulants (NOACs) are preferentially recommended in patients with nonvalvular atrial fibrillation (AF) for stroke prevention over vitamin K antagonists (VKAs). However, the evidence ...regarding the efficacy and safety of NOACs versus VKAs after transcatheter aortic valve implantation (TAVI) in patients with AF is very rare. Pubmed, Embase, Web of science, and Cochrane Databases were searched for eligible studies published before May 19, 2022. A total of 11 studies were included in this meta-analysis involving 27 107 patients. Regarding primary outcomes, there were no differences between NOACs and VKAs in all-cause mortality (RR: 0.84, 95% CI: (0.69, 1.02)) and stroke (RR: 1.00, 95% CI: (0.85, 1.19)). With respect to secondary outcomes, NOACs were associated with reduced incidence of bleeding (RR: 0.77, 95% CI: (0.71, 0.83)) and intracranial bleeding (RR: 0.57, 95% CI: (0.39, 0.83)), whereas no significant differences were found in major or life-threatening bleeding (RR: 0.98, 95% CI: (0.82, 1.17)) and myocardial infarction (RR: 1.37, 95% CI: (0.83, 2.26)). Our meta-analysis revealed the safety and efficacy of NOACs may be superior to VKAs in AF patients undergoing TAVI.
Atrial fibrillation (AF) predisposes patients to the formation of atrial thrombi. The CHA
DS
-VASc score does not include all risk factors for atrial thrombosis. The present study is designed to ...explore the influencing factors of thrombus formation in patients with AF and to investigate the effect of catheter ablation (CA) on recurrent thrombosis in patients with a history of intracardiac thrombus.
(1) This study consisted of 1726 patients that underwent CA, among which 58 patients had a history of intracardiac thrombus prior to CA. The risk factors for thrombus formation were explored by comparing the baseline clinical characteristics of patients with and without atrial thrombus. (2) The left atrial appendage flow velocity (LAAFV) in patients with a history of intracardiac thrombus who were willing to undergo transesophageal echocardiography (TEE) at the latest follow-up were examined, and comparisons of the LAAFV was made before and after CA.
The median follow-up period is 13 months. Persistent AF was found to be the only independent risk factor affecting the formation of atrial thrombus among the investigated factors (OR 3.152; 95%CI 1.806-5.500; p < 0.001). Twenty-seven patients agreed to undergo TEE during follow-up, no clinical ischemic stroke events were recorded, no recurrent intracardiac thrombus formation was detected in patients, 15 patients maintained sinus rhythm (55.6%) during follow-up; successful CA significantly increased LAAFV (difference between latest evaluation prior to CA 17.46 ± 14.81 cm/s, p < 0.001).
Persistent AF is the only independent risk factor for thrombus formation. Successful CA may improve the LAAFV and thereby decrease the risk of intracardiac thrombus formation.
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