Background— Postoperative atrial fibrillation is a frequent complication in cardiac surgery. The aberrant activation of signal transducer and activator transcription 3 (STAT3) contributes to the pathogenesis fibrillation. MicroRNA-21 (miR-21) promotes fibrosis. Recent studies support existence reciprocal regulation between STAT3 miR-21. Here, we test hypothesis that these 2 molecules might form feedback loop postoperative by promoting Methods Results— A sterile pericarditis model was created...

Abstract Aims CD4+ T cells are the major drivers of cardiac-specific autoimmunity in myocarditis, specifically Th1, Treg, and most significant Th17 cells. But molecular mechanisms their activation remain unclear. We aimed to elucidate regulatory role phosphoglycerate kinase 1 (PGK1) experimental autoimmune myocarditis (EAM). Methods results EAM was induced BALB/c mice by subcutaneous injections with alpha myosin heavy chain peptide emulsified complete Freund’s adjuvant. Single-cell...

Post-operative atrial fibrillation (AF) remains a common cause of morbidity. Increasing evidence indicates that inflammation and fibrosis contribute to the pathogenesis this condition. Interleukin (IL)-17A, potent pro-inflammatory cytokine, has been implicated in development number cardiovascular diseases. However, its role post-operative AF unknown. In present study, sterile pericarditis (SP) was induced rats by epicardial application talc. transesophageal burst pacing. Western blot...

A few clinical trials have recently reported the potential effect of colchicine in preventing post-operative atrial fibrillation (POAF) and early (AF) recurrence after catheter pulmonary vein isolation. However, molecular mechanisms through which inhibits AF remain unclear. We aim to assess anti-AF rat sterile pericarditis (SP) model investigate its mechanisms. SP was induced Sprague-Dawley rats by epicardial application talc. Treatment with or vehicle began 1 d before pericardiotomy....

Pre-existing Ca 2+ handling abnormalities constitute the arrhythmogenic substrate in patients developing postoperative atrial fibrillation (POAF), a common complication after cardiac surgery. Postoperative interleukin (IL)-6 levels are associated with fibrosis several animal models of POAF, contributing to arrhythmias. Here, we hypothesize that IL-6-mediated-Ca contribute (AF) sterile pericarditis (SP) rats, an model POAF. SP was induced rats by dusting atria talcum powder. Anti-rat-IL-6...

Transient receptor potential vanilloid 4 (TRPV4) is a Ca2+-permeable nonselective cation channel and can be activated during ischemia/reperfusion (I/R). This study tested whether blockade of TRPV4 alleviate myocardial I/R injury in mice. expression began to increase at 1 h, reached statistically peaked 24-72 h. Treatment with the selective antagonist HC-067047 or knockout markedly ameliorated as demonstrated by reduced infarct size, decreased troponin T levels improved cardiac function 24 h...

Transient receptor potential vanilloid 4 (TRPV4) is highly expressed in heart and vessels can be activated during myocardial ischemia/reperfusion (I/R). Recently, we found that treatment with a selective TRPV4 antagonist HC-067047 significantly reduced infarct size, decreased troponin T levels improved cardiac function murine model I/R. This study was undertaken to investigate the mechanism underlying TRPV4-mediated I/R injury. To mimic injury, established hypoxia/reoxygenation (H/R) H9C2...

Previous studies, including our own, have demonstrated that transient receptor potential vanilloid 4 (TRPV4) is expressed in hearts and implicated cardiac remodeling dysfunction. However, the effects of TRPV4 on pressure overload-induced hypertrophy remain unclear. In this study, we found expression was significantly increased mouse hypertrophic hearts, human failing neurohormone-induced cardiomyocytes. Deletion attenuated transverse aortic constriction (TAC)-induced hypertrophy,...

<b><i>Backgrounds/Aims: </i></b>Acacetin, a natural flavonoid compound, has been proven to exert anti-inflammatory and immunomodulatory effects. Kv1.3 channels, highly expressed in human T cells, are attractive therapeutic targets treat inflammatory immunological disorders. The present study was designed characterize the inhibition of channels by Acacetin cells examine its role cell activation. <b><i>Methods: </i></b>Whole-cell patch-clamp applied record K_Ca currents cells;...

Antioxidative stress provides a cardioprotective effect during myocardial ischemia/reperfusion (I/R). Previous research has demonstrated that the blockade of transient receptor potential vanilloid 4 (TRPV4) attenuates I/R injury. However, underlying mechanism remains unclear. The current study is aimed at investigating antioxidative activity TRPV4 inhibition and elucidating mechanisms in vitro ex vivo. We found inhibiting by selective blocker HC-067047 or specific TRPV4-siRNA significantly...

Ca2+ entry via the transient receptor potential vanilloid 4 (TRPV4) channel contributes to overload and triggers many pathophysiological conditions, including myocardial ischemia/reperfusion (I/R) injury. Propofol, a widely used intravenous anesthetic, attenuates I/R However, mechanism of propofol remains be examined. The present study aims test hypothesis that injury through suppression TRPV4. We murine ex vivo model in vitro cultured myocytes subjected hypoxia/reoxygenation (H/R). Propofol...

Atrial fibrillation (AF) commonly occurs after surgery and is associated with atrial remodeling. TRPV4 functionally expressed in the heart, its activation affects cardiac structure functions. We hypothesized that blockade alleviates remodeling reduces AF induction sterile pericarditis (SP) rats. antagonist GSK2193874 or vehicle was orally administered 1 day before pericardiotomy. susceptibility function were assessed using vivo electrophysiology, ex optical mapping, patch clamp, molecular...

Abstract Lovastatin is a member of Statins, which are beneficial in lot immunologic cardiovascular diseases and T cell-mediated autoimmune diseases. Kv1.3 channel plays important roles the activation proliferation cells have become attractive target for immune-related disorders. The present study was designed to examine block effect on human clarify its new immunomodulatory mechanism. We found that inhibited currents concentration- voltage-dependent manner IC50 peak, end pulse 39.81 ± 5.11,...

Background: Septic Acute Lung Injury (SALI)-induced severe respiratory dysfunction has been established to significantly increase patient mortality rates and socioeconomic costs. To mitigate cellular damage, autophagy —a conserved biological process in organisms —degrades damaged components, such as proteins organelles. Although is crucially involved the inflammatory response, its precise molecular mechanisms SALI remain unclear, forming basis of this study. Methods: Herein, two microarray...

Diphenyl phosphine oxide-1 (DPO-1) is a potent Kv1.5 channel inhibitor that has therapeutic potential for the treatment of atrial fibrillation. Many other blockers also potently inhibit Kv1.3 channel, but whether DPO-1 blocks channels not been investigated. The highly expressed in activated T cells, which considered favorable target immunomodulation. Accordingly, we hypothesized may exert immunosuppressive and anti-inflammatory effects by inhibiting activity. In this study, blocked current...

Abstract The Ca2+-permeable TRPV4 cation channel is expressed in neutrophils and contributes to myocardial ischemia/reperfusion injury. Here we tested the hypotheses that promotes neutrophil activation subsequently aggregates protein was confirmed neutrophils, its function assessed by current intracellular Ca2+ concentration elevations evoked agonists. Furthermore, agonists dose-dependently promoted migration toward fMLP, reactive oxygen species production, myeloperoxidase release, which...

Hypoxia-inducible factor-1 (HIF-1) regulates the expression of hypoxia-inducible genes by binding erythropoietin (EPO) enhancer fragments. Of these genes, HIF-1 upregulates voltage-gated K+1.2 channels (Kv1.2) in rat PC12 cells. Whether hypoxia-induced Kv channel cultured pulmonary artery smooth muscle cells (PASMCs), however, has not been determined. In this study, we investigated effects hypoxia on Kv1.2 Kv1.5, Kv2.1, and Kv9.3 PASMCs examined direct role transfecting either wild type or...

Imatinib mesylate (IM), a widely prescribed powerful tyrosine kinase inhibitor, has been associated with increased risk of heart failure and is known to induce cell apoptosis death in isolated cardiomyocytes. In addition acquired long QT syndrome, pharmacological inhibition human ether-à-go-go-related gene (HERG) channel reported involve apoptosis. The present study was undertaken characterize the biophysical properties IM on HERG molecular determinants blockade using mutant channels (Y652A...

Previous studies, including our own, have demonstrated that transient receptor potential vanilloid 4 (TRPV4) is involved in myocardial ischemia-reperfusion (IR) injury, yet its underlying molecular mechanism remains unclear. In this study, we isolated mice hearts for a Langendorff perfusion test and used HL-1 myocytes vitro assessments. We first confirmed TRPV4 agonist (GSK101) enhanced IR as by the reduced recovery of cardiac function, larger infarct size, more apoptotic cells. also found...