Exercise mitigates reductive stress-induced cardiac remodeling in mice.

The endoplasmic reticulum (ER) regulates protein folding and maintains proteostasis in cells. We observed that the ER transcriptome is impaired during chronic reductive stress (RS) in cardiomyocytes. Here, we hypothesized that a prolonged moderate treadmill exercise mitigates the RS-induced ER dysfunction and cardiac remodeling in cardiac-specific constitutively active Nrf2 mice (CaNrf2-TG).

Structurally constrained and pathology-aware convolutional transformer generative adversarial network for virtual histology staining of human coronary optical coherence tomography images.

Significance: There is a significant need for the generation of virtual histological information from coronary optical coherence tomography (OCT) images to better guide the treatment of coronary artery disease (CAD). However, existing methods either require a large pixel-wise paired training dataset or have limited capability to map pathological regions.

Aim: The aim of this work is to generate virtual histological information from coronary OCT images, without a pixel-wise paired training dataset while capable of providing pathological patterns.

The interplay between sex, time of day, fasting status, and their impact on cardiac mitochondrial structure, function, and dynamics.

Mitochondria morphology and function, and their quality control by mitophagy, are essential for heart function. We investigated whether these are influenced by time of the day (TOD), sex, and fed or fasting status, using transmission electron microscopy (EM), mitochondrial electron transport chain (ETC) activity, and mito-QC reporter mice. We observed peak mitochondrial number at ZT8 in the fed state, which was dependent on the intrinsic cardiac circadian clock, as hearts from cardiomyocyte-specific BMAL1 knockout (CBK) mice exhibit different TOD responses.

Toward reliable calcification detection: calibration of uncertainty in object detection from coronary optical coherence tomography images.

Significance: Optical coherence tomography (OCT) has become increasingly essential in assisting the treatment of coronary artery disease (CAD). However, unidentified calcified regions within a narrowed artery could impair the outcome of the treatment. Fast and objective identification is paramount to automatically procuring accurate readings on calcifications within the artery.

Cardiac and Pulmonary Histopathology in Baboons Following Genetically-Engineered Pig Orthotopic Heart Transplantation.

BACKGROUND Although improving, survival after pig orthotopic heart transplantation (OHTx) in baboons has been mixed and largely poor. The causes for the high incidence of early failure remain uncertain. MATERIAL AND METHODS We have carried out pig OHTx in 4 baboons.

Multi-Scale Reconstruction of Undersampled Spectral-Spatial OCT Data for Coronary Imaging Using Deep Learning.

Coronary artery disease (CAD) is a cardiovascular condition with high morbidity and mortality. Intravascular optical coherence tomography (IVOCT) has been considered as an optimal imagining system for the diagnosis and treatment of CAD. Constrained by Nyquist theorem, dense sampling in IVOCT attains high resolving power to delineate cellular structures/features.

Use of Telepathology to Facilitate COVID-19 Research and Education through an Online COVID-19 Autopsy Biorepository.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has increased the use of technology for communication including departmental conferences, working remotely, and distance teaching. Methods to enable these activities should be developed and promulgated.

Objective: To repurpose a preexisting educational website to enable the development of a COVID-19 autopsy biorepository to support distance teaching and COVID-19 research.

Cardiac pathology in COVID-19: a single center autopsy experience.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is commonly associated with myocardial injury and heart failure. The pathophysiology behind this phenomenon remains unclear, with many diverse and multifaceted hypotheses. To contribute to this understanding, we describe the underlying cardiac findings in fifty patients who died with coronavirus disease 2019 (COVID-19).

Mitochondrial Morphology and Mitophagy in Heart Diseases: Qualitative and Quantitative Analyses Using Transmission Electron Microscopy.

Transmission electron microscopy (TEM) has long been an important technique, capable of high degree resolution and visualization of subcellular structures and organization. Over the last 20 years, TEM has gained popularity in the cardiovascular field to visualize changes at the nanometer scale in cardiac ultrastructure during cardiovascular development, aging, and a broad range of pathologies. Recently, the cardiovascular TEM enabled the studying of several signaling processes impacting mitochondrial function, such as mitochondrial fission/fusion, autophagy, mitophagy, lysosomal degradation, and lipophagy.

Cerebellar talcosis following posterior reversible encephalopathy syndrome in an intravenous methamphetamine abuser.

Background: Intravenous (IV) methamphetamine abuse is associated with a variety of short- and long-term effects on the nervous system, some of which have yet to be fully elucidated. One known systemic complication that has not been described in nervous system tissues is the deposition of substrate crystals contained in injectable drugs.

Case Description: An unusual case is presented of a 35-year-old active IV methamphetamine abuser with posterior reversible encephalopathy syndrome (PRES) who subsequently developed multifocal bilateral cerebellar enhancing lesions and leptomeningeal enhancement due to biopsy-proven crystalline deposits.

Assessment of ICAM-1 N-glycoforms in mouse and human models of endothelial dysfunction.

Endothelial dysfunction is a critical event in vascular inflammation characterized, in part, by elevated surface expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1). ICAM-1 is heavily N-glycosylated, and like other surface proteins, it is largely presumed that fully processed, complex N-glycoforms are dominant. However, our recent studies suggest that hypoglycosylated or high mannose (HM)-ICAM-1 N-glycoforms are also expressed on the cell surface during endothelial dysfunction, and have higher affinity for monocyte adhesion and regulate outside-in endothelial signaling by different mechanisms.

Evolution of Immune Checkpoint Blockade-Induced Myocarditis Over 2 Years.

Ipilimumab and nivolumab for melanoma induced smoldering myocarditis remitting with steroids. Rechallenge with nivolumab produced steroid-refractory myocarditis confirmed by electron microscopy. Tacrolimus and mycophenolate transiently reduced inflammation, but antithymocyte globulin induced remission.

Reductive Stress Causes Pathological Cardiac Remodeling and Diastolic Dysfunction.

Redox homeostasis is tightly controlled and regulates key cellular signaling pathways. The cell's antioxidant response provides a natural defense against oxidative stress, but excessive antioxidant generation leads to reductive stress (RS). This study elucidated how chronic RS, caused by constitutive activation of nuclear erythroid related factor-2 (caNrf2)-dependent antioxidant system, drives pathological myocardial remodeling.

Progressive cardiac arrhythmias and ECG abnormalities in the Huntington's disease BACHD mouse model.

Huntington's disease (HD) is a dominantly inherited neurodegenerative disease. There is accumulating evidence that HD patients have increased prevalence of conduction abnormalities and compromised sinoatrial node function which could lead to increased risk for arrhythmia. We used mutant Huntingtin (mHTT) expressing bacterial artificial chromosome Huntington's disease mice to determine if they exhibit electrocardiogram (ECG) abnormalities involving cardiac conduction that are known to increase risk of sudden arrhythmic death in humans.

Exercise Mediated Nrf2 Signaling Protects the Myocardium From Isoproterenol-Induced Pathological Remodeling.

Although exercise derived activation of Nrf2 signaling augments myocardial antioxidant signaling, the molecular mechanisms underlying the benefits of moderate exercise training (MET) in the heart remain elusive. Here we hypothesized that exercise training stabilizes Nrf2-dependent antioxidant signaling, which then protects the myocardium from isoproterenol-induced damage. The present study assessed the effects of 6 weeks of MET on the Nrf2/antioxidant function, glutathione redox state, and injury in the myocardium of C57/BL6J mice that received isoproterenol (ISO; 50 mg/kg/day for 7 days).

Enhanced Keap1-Nrf2 signaling protects the myocardium from isoproterenol-induced pathological remodeling in mice.

Nuclear factor (erythroid-derived 2)-like 2 (NFE2L2/Nrf2) is an inducible transcription factor that is essential for maintenance of redox signaling in response to stress. This suggests that if Nrf2 expression response could be enhanced for a defined physiological pro-oxidant stress then it would be protective. This has important implications for the therapeutic manipulation of the Keap1/Nrf2 signaling pathway which is now gaining a lot of attention.

Novel role of the ER/SR Ca sensor STIM1 in the regulation of cardiac metabolism.

The endoplasmic reticulum/sarcoplasmic reticulum Ca sensor stromal interaction molecule 1 (STIM1), a key mediator of store-operated Ca entry, is expressed in cardiomyocytes and has been implicated in regulating multiple cardiac processes, including hypertrophic signaling. Interestingly, cardiomyocyte-restricted deletion of STIM1 (STIM1-KO) results in age-dependent endoplasmic reticulum stress, altered mitochondrial morphology, and dilated cardiomyopathy in mice. Here, we tested the hypothesis that STIM1 deficiency may also impact cardiac metabolism.

Myocardial rupture after small acute myocardial infarction in the absence of coronary artery disease.

A 73-year-old woman with a past medical history of hypertension suffered a cardiac arrest. After successful resuscitation, she was hypotensive and tachycardic and the ECG showed ST elevation in the inferior and lateral precordial leads. Coronary angiography did not show evidence of obstructive coronary artery disease.

Association of Preexisting Arterial Intimal Hyperplasia with Arteriovenous Fistula Outcomes.

Background And Objectives: Preoperative arterial function is associated with arteriovenous fistula (AVF) development. Because arterial pathology may correlate with its function, preexisting arterial intimal hyperplasia may be associated with AVF development.

Design, Setting, Participants, & Measurements: Vascular specimens obtained from 125 patients (with minimal 2 mm arterial diameter and 2.

Genome-wide DNA methylation encodes cardiac transcriptional reprogramming in human ischemic heart failure.

Ischemic cardiomyopathy (ICM) is the clinical endpoint of coronary heart disease and a leading cause of heart failure. Despite growing demands to develop personalized approaches to treat ICM, progress is limited by inadequate knowledge of its pathogenesis. Since epigenetics has been implicated in the development of other chronic diseases, the current study was designed to determine whether transcriptional and/or epigenetic changes are sufficient to distinguish ICM from other etiologies of heart failure.

Idiopathic Ventricular Arrhythmias Originating From the Infundibular Muscles: Prevalence, Electrocardiographic and Electrophysiological Characteristics, and Outcome of Catheter Ablation.

Background: This study investigated the prevalence, electrocardiographic and electrophysiological characteristics, and ablation outcome of idiopathic ventricular arrhythmias (VAs) originating from the infundibular muscles (IFMs) in the right ventricle consisting of the parietal band (PB) and septal band (SB).

Methods And Results: We studied 19 patients with idiopathic VA origins in the PB in 14 and SB in 5 among 294 consecutive patients with VA origins in the right ventricle. PB and SB VAs exhibited left bundle branch block with a left inferior (n=12) or superior (n=2) axis and left (n=4) or right inferior (n=1) axis pattern, respectively.

Abnormalities of vascular histology and collagen fiber configuration in patients with advanced chronic kidney disease.

Introduction:: Several histologic features have been identified in the upper-extremity arteries and veins of patients with advanced chronic kidney disease, which may affect arteriovenous fistula maturation. However, it is unclear whether these chronic kidney disease vascular features are abnormal.

Methods:: We obtained upper-extremity arterial and venous specimens from 125 advanced chronic kidney disease patients undergoing arteriovenous fistula creation and from 15 control subjects.

Smoldering myocarditis following immune checkpoint blockade.

Background: Severe myocarditis associated with electrical conduction abnormalities and occasionally heart failure has been well documented following treatment with immune checkpoint blockade with an estimated incidence of less than 1%. However, the incidence, early detection, and management of less severe immune-related myocarditis are unknown since most immunotherapy trials have not included routine cardiac monitoring. Herein, we provide the first description of subclinical or smoldering myocarditis with minimal signs and symptoms following immune checkpoint blockade with a single dose of ipilimumab and nivolumab.

Idiopathic Ventricular Arrhythmias Originating From the Parietal Band: Electrocardiographic and Electrophysiological Characteristics and Outcome of Catheter Ablation.

Backgrounds: The parietal band is one of the muscle bands in the right ventricle. This study investigated the electrocardiographic and electrophysiological characteristics and ablation outcome of idiopathic ventricular arrhythmias (VAs) originating from the parietal band.

Methods And Results: We studied 14 patients with idiopathic VA origins in the parietal band among 294 consecutive patients with VA origins in the right ventricle.