PIEZO1 mediates a mechanothrombotic pathway in diabetes.

Thrombosis is the leading complication of common human disorders including diabetes, coronary heart disease, and infection and remains a global health burden. Current anticoagulant therapies that target the general clotting cascade are associated with unpredictable adverse bleeding effects, because understanding of hemostasis remains incomplete. Here, using perturbational screening of patient peripheral blood samples for latent phenotypes, we identified dysregulation of the major mechanosensory ion channel Piezo1 in multiple blood lineages in patients with type 2 diabetes mellitus (T2DM).

Tbx18 promoted the conversion of human-induced pluripotent stem cell-derived cardiomyocytes into sinoatrial node-like pacemaker cells.

Sinoatrial node (SAN) pacemaker cells originate from T-box transcription factor 18 (Tbx18)-expressing progenitor cells. The present study aimed to investigate whether overexpression of human transcription factor Tbx18 could reprogram human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) into SAN-like pacemaker cells (SANLPCs) in vitro. In the study, hiPSCs were first differentiated into hiPSC-CMs through regulating the Wnt/β-catenin pathway, then purified hiPSC-CMs were transfected by Tbx18 adenovirus (Tbx18-CMs group) or green fluorescent protein (GFP) adenovirus (GFP-CMs group).

Daphnetin Preconditioning Decreases Cardiac Injury and Susceptibility to Ventricular Arrhythmia following Ischaemia-Reperfusion through the TLR4/MyD88/NF-Κb Signalling Pathway.

Background/aims: Daphnetin (7,8-dihydroxycoumarin, DAP) exhibits various bioactivities, such as anti-inflammatory and antioxidant activities. However, the role of DAP in myocardial ischaemia/reperfusion (I/R) injury and I/R-related arrhythmia is still uncertain. This study aimed to investigate the mechanisms underlying the effects of DAP on myocardial I/R injury and electrophysiological properties in vivo and in vitro.

Selective chemical ablation of transient receptor potential vanilloid 1 expressing neurons in the left stellate ganglion protects against ischemia-induced ventricular arrhythmias in dogs.

Objectives: Findings from prior investigations show that left stellate ganglion (LSG) inhibitory approaches protect the heart from ventricular arrhythmias (VAs) caused by acute myocardial infarction (AMI), which still remain many side effects. Targeted transient receptor potential vanilloid 1/tyrosine hydroxylase (TRPV-1/TH) expressing sympathetic neurons ablation is a novel neuro-ablative strategy. The aim of this investigation was to explore if targeted molecular neuro-ablative strategy by resiniferatoxin (RTX) stellate microinjection could protect against ischemia-induced VAs.

Cardiac Sympathetic Afferent Denervation Protects Against Ventricular Arrhythmias by Modulating Cardiac Sympathetic Nerve Activity During Acute Myocardial Infarction.

BACKGROUND Augmented cardiac sympathetic afferent reflex (CSAR) plays a role in enhanced sympathetic activity. Given that a strategy for abolishing augmented CSAR-induced sympathetic activation may be beneficial for protecting against ventricular arrhythmias (VAs) triggered by acute myocardial infarction (AMI), we investigated whether cardiac sympathetic afferent denervation (CSAD) could protect against VAs by modulating cardiac sympathetic nerve activity in an AMI dog model. MATERIAL AND METHODS Twenty-two anesthetized dogs were assigned to the CSAD group (n=9) and the sham group (n=13) randomly.

In vitro study of the effects of reprogramming neonatal rat fibroblasts transfected with TBX18 on spontaneous beating in neonatal rat cardiomyocytes.

Intracardiac injection of the growth‑promoting transcription factor of the sinoatrial node T‑box18 (TBX18) has been shown to reprogram cardiomyocytes into induced sinoatrial nodes that produce high‑frequency and neuroregulated ectopic beats. Fibroblasts, the most important non‑cardiomyocyte cell type in the heart, can affect the electrophysiological properties of cardiomyocytes by electrically coupling with them. The aim of the present study was to explore the reprogramming of cardiac fibroblasts (CFs) transfected with TBX18 in vitro and observe its effect on the pacing frequency of neonatal rat ventricular cardiomyocytes (NRVMs) in a co‑culture system.

YY1-induced upregulation of lncRNA KCNQ1OT1 regulates angiotensin II-induced atrial fibrillation by modulating miR-384b/CACNA1C axis.

Recent years, the role of long non-coding RNAs (lncRNAs) in atrial fibrillation (AF) has been gradually elucidated. In the current study, we measured the expression of ten AF-related lncRNAs to do qRT-PCR analysis. LncRNA KCNQ1 overlapping transcript 1 (KCNQ1OT1) was found to be significantly upregulated in AF model and Ang-II-induced mice heart.

Targeted ablation of cardiac sympathetic neurons attenuates adverse postinfarction remodelling and left ventricular dysfunction.

New Findings: What is the central question of this study? Can targeted ablation of cardiac sympathetic neurons suppress myocardial infarction-induced adverse cardiac remodelling and left ventricular dysfunction? What is the main finding and its importance? Targeted ablation of cardiac sympathetic neurons significantly alleviated sympathetic remodelling and neuroendocrine activation, attenuated cardiac hypertrophy and fibrosis and improved left ventricular function. Thus, targeted ablation of cardiac sympathetic neurons might have a beneficial effect on adverse postinfarction remodelling and left ventricular dysfunction.

Abstract: Sympathetic overactivation is crucial in the development and progression of adverse cardiac remodelling and dysfunction.

Targeted ablation of cardiac sympathetic neurons improves ventricular electrical remodelling in a canine model of chronic myocardial infarction.

Aims: The purpose of this study was to evaluate the cardiac electrophysiologic effects of targeted ablation of cardiac sympathetic neurons (TACSN) in a canine model of chronic myocardial infarction (MI).

Methods And Results: Thirty-eight anaesthetized dogs were randomly assigned into the sham-operated, MI, and MI-TACSN groups, respectively. Myocardial infarction-targeted ablation of cardiac sympathetic neuron was induced by injecting cholera toxin B subunit-saporin compound in the left stellate ganglion (LSG).

Role of CaMKII in free fatty acid/hyperlipidemia-induced cardiac remodeling both in vitro and in vivo.

Rationale: The cellular mechanisms of obesity/hyperlipidemia-induced cardiac remodeling are many and not completely elucidated. Ca/calmodulin-dependent protein kinase II (CaMKII), a multifunctional serine/threonine kinase, has been reported to be involved in a variety of cardiovascular diseases. However, its role in obesity/hyperlipidemia-induced cardiac remodeling is still unknown.

CaMKII Activation Promotes Cardiac Electrical Remodeling and Increases the Susceptibility to Arrhythmia Induction in High-fat Diet-Fed Mice With Hyperlipidemia Conditions.

Background: Obesity/hyperlipidemia is closely related to both atrial and ventricular arrhythmias. CaMKII, a multifunctional serine/threonine kinase, has been involved in cardiac arrhythmias of different etiologies. However, its role in obesity/hyperlipidemia-related cardiac arrhythmia is unexplored.

Novel Protective Role of Myeloid Differentiation 1 in Pathological Cardiac Remodelling.

Myeloid differentiation 1 (MD-1), a secreted protein interacting with radioprotective 105 (RP105), plays an important role in Toll-like receptor 4 (TLR4) signalling pathway. Previous studies showed that MD-1 may be restricted in the immune system. In this study, we demonstrated for the first time that MD-1 was highly expressed in both human and animal hearts.

Predictors of late atrial fibrillation recurrence after cryoballoon-based pulmonary vein isolation: a meta-analysis.

Background: The recurrence rate of atrial fibrillation (AF) after cryoballoon ablation in drug refractory AF patients is high. Late-recurrence of AF has various predictors.

Aim: The aim of the study was to explore the related risk factors that can effectively predict late AF recurrence after cryoballoon-based pulmonary vein isolation.

Regulator of G-protein signaling 5 protects cardiomyocytes against apoptosis during in vitro cardiac ischemia-reperfusion in mice by inhibiting both JNK1/2 and P38 signaling pathways.

Ischemic heart disease is one of the most common diseases in modern society. Ischemic myocardium can be salvaged by vascular recanalization therapy, but its benefit is attenuated by injury that can occur during reperfusion. And apoptotic cell death plays an important part in myocardial ischemia-reperfusion (IR) injury.