PANoptosis is a prominent cell death feature in thoracic aortic aneurysm or dissection.

Thoracic aortic aneurysm and dissection (TAAD) is a devastating macrovascular disease, and its pathogenic mechanisms have not been well clarified. This study aimed to investigate the role of PANoptosis, which is newly defined programmed cell death (PCD) and characterized by pyroptosis, apoptosis, and necroptosis, in the pathogenesis of TAAD. We found that the expression of initiator factor Z-DNA binding protein 1 (ZBP1) and PANoptosis-related genes were upregulated in the β-aminopropionitrile (BAPN) + Angiotensin II (Ang II)-induced TAAD mice.

Genetic inactivation of β-catenin is salubrious, whereas its activation is deleterious in desmoplakin cardiomyopathy.

Aims: Mutations in the DSP gene encoding desmoplakin, a constituent of the desmosomes at the intercalated discs (IDs), cause a phenotype that spans arrhythmogenic cardiomyopathy (ACM) and dilated cardiomyopathy. It is typically characterized by biventricular enlargement and dysfunction, myocardial fibrosis, cell death, and arrhythmias. The canonical wingless-related integration (cWNT)/β-catenin pathway is implicated in the pathogenesis of ACM.

A Systematic Analysis of the Clinical Outcome Associated with Multiple Reclassified Desmosomal Gene Variants in Arrhythmogenic Right Ventricular Cardiomyopathy Patients.

The presence of multiple pathogenic variants in desmosomal genes (DSC2, DSG2, DSP, JUP, and PKP2) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been linked to a severe phenotype. However, the pathogenicity of variants is reclassified frequently, which may result in a changed clinical risk prediction. Here, we present the collection, reclassification, and clinical outcome correlation for the largest series of ARVC patients carrying multiple desmosomal pathogenic variants to date (n = 331).

Engineering of MSCs sheet for the prevention of myocardial ischemia and for left ventricle remodeling.

Tissue engineering combines cell biology and material science to construct tissues or organs for disease modeling, drug testing, and regenerative medicine. The cell sheet is a newly developed tissue engineering technology that has brought about scaffold-free tissue and shows great application potential. In this review, we summarized recent progress and future possibilities in preclinical research into and clinical applications of cell sheets fabricated by differing cell types from various sources for cardiac tissue repair, and the manufacturing strategies and promising application potential of 3D cell-dense tissue constructed from cell sheets.

PANoptosis is a prominent feature of desmoplakin cardiomyopathy.

Introduction: Arrhythmogenic cardiomyopathy (ACM) is hereditary cardiomyopathy caused by pathogenic variants (mutations) in genes encoding the intercalated disc (ID), particularly desmosome proteins. ACM caused by mutations in the gene encoding desmoplakin (DSP) is characterized by the prominence of cell death, myocardial fibrosis, and inflammation, and is referred to as desmoplakin cardiomyopathy.

Aim: The aim of this article was to gain insight into the pathogenesis of DSP cardiomyopathy.

The WNT/β-catenin pathway regulates expression of the genes involved in cell cycle progression and mitochondrial oxidative phosphorylation in the postmitotic cardiac myocytes.

Introduction: Aging is associated with cardiac myocyte loss, sarcopenia, and cardiac dysfunction. Adult cardiac myocytes are postmitotic cells with an insufficient proliferative capacity to compensate for myocyte loss. The canonical WNT (cWNT) pathway is involved in the regulation of cell cycle reentry in various cell types.

Effects of tamoxifen inducible MerCreMer on gene expression in cardiac myocytes in mice.

The Cre-LoxP technology, including the tamoxifen (TAM) inducible MerCreMer (MCM), is increasingly used to delineate gene function, understand the disease mechanisms, and test therapeutic interventions. We set to determine the effects of TAM-MCM on cardiac myocyte transcriptome. Expression of the MCM was induced specifically in cardiac myocytes upon injection of TAM to myosin heavy chain 6-MCM () mice for 5 consecutive days.

Cardiac deceleration capacity as an indicator for cardioneuroablation in patients with refractory vasovagal syncope.

Background: Cardioneuroablation is an emerging therapy for refractory vasovagal syncope (VVS), but the standard enrollment criterion is undetermined. Mainstream studies empirically enroll patients with cardioinhibitory and mixed types of VVS on the basis of the head-up tilt (HUT). However, a variety of studies have shown that the results of HUT exhibit unpleasant reproducibility.

A scalable coaxial bioprinting technology for mesenchymal stem cell microfiber fabrication and high extracellular vesicle yield.

Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are promising candidates for regenerative medicine; however, the lack of scalable methods for high quantity EV production limits their application. In addition, signature EV-derived proteins shared in 3D environments and 2D surfaces, remain mostly unknown. Herein, we present a platform combining MSC microfiber culture with ultracentrifugation purification for high EV yield.

Pharmacological suppression of the WNT signaling pathway attenuates age-dependent expression of the phenotype in a mouse model of arrhythmogenic cardiomyopathy.

Introduction: Arrhythmogenic cardiomyopathy (ACM) is a genetic disease of the myocardium, characterized by cardiac arrhythmias, dysfunction, and sudden cardiac death. The pathological hallmark of ACM is fibro-adipocytes replacing cardiac myocytes. The canonical WNT pathway is implicated in the pathogenesis of ACM.

The EP300/TP53 pathway, a suppressor of the Hippo and canonical WNT pathways, is activated in human hearts with arrhythmogenic cardiomyopathy in the absence of overt heart failure.

Aims: Arrhythmogenic cardiomyopathy (ACM) is a primary myocardial disease that typically manifests with cardiac arrhythmias, progressive heart failure, and sudden cardiac death (SCD). ACM is mainly caused by mutations in genes encoding desmosome proteins. Desmosomes are cell-cell adhesion structures and hubs for mechanosensing and mechanotransduction.

Single-Cell RNA Sequencing Uncovers Paracrine Functions of the Epicardial-Derived Cells in Arrhythmogenic Cardiomyopathy.

Background: Arrhythmogenic cardiomyopathy (ACM) manifests with sudden death, arrhythmias, heart failure, apoptosis, and myocardial fibro-adipogenesis. The phenotype typically starts at the epicardium and advances transmurally. Mutations in genes encoding desmosome proteins, including DSP (desmoplakin), are major causes of ACM.

Haploinsufficiency of Tmem43 in cardiac myocytes activates the DNA damage response pathway leading to a late-onset senescence-associated pro-fibrotic cardiomyopathy.

Aims: Arrhythmogenic cardiomyopathy (ACM) encompasses a genetically heterogeneous group of myocardial diseases whose manifestations are sudden cardiac death, cardiac arrhythmias, heart failure, and in a subset fibro-adipogenic infiltration of the myocardium. Mutations in the TMEM43 gene, encoding transmembrane protein 43 (TMEM43) are known to cause ACM. The purpose of the study was to gain insights into the molecular pathogenesis of ACM caused by TMEM43 haploinsufficiency.

Catheter ablation of arrhythmogenic right ventricular cardiomyopathy ventricular tachycardia: 18-year experience in 284 patients.

Aims: The study aims to describe the long-term outcome of radiofrequency catheter ablation for ventricular tachycardia (VT) in a large cohort arrhythmogenic right ventricular cardiomyopathy (ARVC) patients.

Methods And Results: Radiofrequency catheter ablation was performed in 284 ARVC patients due to VT between July 2000 and January 2019. An endocardial approach was used initially, with epicardial ablation procedures reserved for those patients who failed an endocardial ablation.

Effect of Pregnancy in Arrhythmogenic Right Ventricular Cardiomyopathy.

Less is known about pregnancy in women with arrhythmogenic right ventricular cardiomyopathy (ARVC). From April 1995 to May 2018, 157 women with ARVC were retrospectively enrolled. Data on pregnancy and cardiac outcomes were analyzed.

Exercise restores dysregulated gene expression in a mouse model of arrhythmogenic cardiomyopathy.

Aims: Arrhythmogenic cardiomyopathy (ACM) is a myocardial disease caused mainly by mutations in genes encoding desmosome proteins ACM patients present with ventricular arrhythmias, cardiac dysfunction, sudden cardiac death, and a subset with fibro-fatty infiltration of the right ventricle predominantly. Endurance exercise is thought to exacerbate cardiac dysfunction and arrhythmias in ACM. The objective was to determine the effects of treadmill exercise on cardiac phenotype, including myocyte gene expression in myocyte-specific desmoplakin (Dsp) haplo-insufficient (Myh6-Cre:DspW/F) mice.

Efficacy of Nifekalant in Patients With Wolff-Parkinson-White Syndrome and Atrial Fibrillation: Electrophysiological and Clinical Findings.

Background The efficacy of nifekalant in preexcited atrial fibrillation ( AF ) has not been assessed. Methods and Results The study populations consisted of patients with sustained preexcited AF (n=51), paroxysmal supraventricular tachycardia (n=201), and persistent AF (n=87). Effects of intravenous infusion of nifekalant were assessed on electrophysiological and clinical parameters.

Bradyarrhythmias in Arrhythmogenic Right Ventricular Cardiomyopathy.

Less is known about bradyarrhythmias in arrhythmogenic right ventricular cardiomyopathy (ARVC). This cross-sectional study aimed to assess the prevalence and clinical significance of bradyarrhythmias in ARVC. From May 1995 to December 2017, bradyarrhythmias including sick sinus syndrome, atrioventricular block, and intraventricular conductional block (ICB) were investigated in 522 ARVC patients.

Relation of Left Atrial Appendage Morphology Determined by Computed Tomography to Prior Stroke or to Increased Risk of Stroke in Patients With Atrial Fibrillation.

Left atrial appendage (LAA) morphology is considered to be associated with ischemic stroke, non-Chicken Wing LAA morphology increases the risk of thromboembolic events. However, existing classification of LAA morphology remains not well quantifiable and therefore may leave room for substantial subjective interpretation. This study aimed to assess interobserver and intraobserver agreements in LAA morphology and its real value in stroke prediction.

Thyroid-stimulating hormone within the normal range and risk of major adverse cardiovascular events in nonischemic dilated cardiomyopathy patients with severe left ventricular dysfunction.

Background: The association between thyroid-stimulating-hormone (TSH) and prognosis of nonischemic dilated cardiomyopathy (NIDCM) in patients with normal thyroid function remains unclear.

Hypothesis: Our aim was to investigate the association between TSH and major adverse cardiovascular events in euthyroid NIDCM patients.

Methods: The original cohort consisted of 216 consecutive euthyroid NIDCM patients, with left ventricular ejection fraction (LVEF) ≤35%, who were observed from 2010 to 2013.

Atrial involvement in arrhythmogenic right ventricular cardiomyopathy patients referred for ventricular arrhythmias ablation.

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable myocardium disorder that predominantly affects the ventricle. Little is known about atrial involvement. This study aimed to assess atrial involvement, especially the role of genotype on atrium in ARVC.

Chemical constituents from Gnaphalium affine and their xanthine oxidase inhibitory activity.

Gnaphalium affine D. Don, a medicinal and edible plant, has been used to treat gout in traditional Chinese medicine and popularly consumed in China for a long time. A detailed phytochemical investigation on the aerial part of G.