A5034149986- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Atrial Fibrillation Management and Outcomes
- Neuroscience and Neural Engineering
- Hormonal Regulation and Hypertension
- Cardiac Arrhythmias and Treatments
- Epigenetics and DNA Methylation
- Receptor Mechanisms and Signaling
- Endoplasmic Reticulum Stress and Disease
- Vitamin C and Antioxidants Research
- Signaling Pathways in Disease
- Cardiac Fibrosis and Remodeling
- Cardiac pacing and defibrillation studies
- ECG Monitoring and Analysis
- Corrosion Behavior and Inhibition
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- S100 Proteins and Annexins
- Neuroscience and Neuropharmacology Research
- Peptidase Inhibition and Analysis
- Galectins and Cancer Biology
- Ubiquitin and proteasome pathways
- Muscle activation and electromyography studies
- Synthesis and pharmacology of benzodiazepine derivatives
- MicroRNA in disease regulation
- Atherosclerosis and Cardiovascular Diseases
Regional West Medical Center
2023
University of Michigan
2015-2023
McGill University
2018
The University of Tokyo
2018
West German Heart and Vascular Center Essen
2018
Brown University
2018
Center for Research and Advanced Studies of the National Polytechnic Institute
2007-2016
Instituto Politécnico Nacional
2007-2016
University of Rochester Medical Center
2016
New York University
2016
Atrial fibrillation (AF) usually starts as paroxysmal but can evolve relentlessly to the persistent and permanent forms. However, mechanisms governing such a transition are unknown. The authors show that intracardiac serum levels of galectin (Gal)-3 greater in patients with than AF Gal-3 independently predicts atrial tachyarrhythmia recurrences after single ablation procedure. Using sheep model further demonstrate upstream therapy targeting diminishes both electrical remodeling fibrosis by...
During physical exercise or stress, the sympathetic system stimulates cardiac contractility via β-adrenergic receptor (β-AR) activation, resulting in protein kinase A (PKA)-mediated phosphorylation of ryanodine RyR2. PKA-dependent "hyperphosphorylation" RyR2 channel has been proposed as a major impairment that contributes to progression heart failure. However, sites PKA and their status diseases are not well defined. Among known sites, serine 2030 (S2030) remains highly controversial site...
Significance Tbx20 is a transcription factor whose critical role in cardiogenesis well-established. Here we functionally analyzed the electrophysiological effects produced by mutation (p.R311C) found some affected individuals belonging to family with long QT syndrome (an inherited cardiac arrhythmia due delayed ventricular repolarization). We demonstrated that selectively increases expression of KCNH2 , which encodes for channel Kv11.1 (hERG) generates main repolarizing current. Conversely,...
Mutations in SCN2B, encoding voltage-gated sodium channel β2-subunits, are associated with human cardiac arrhythmias, including atrial fibrillation and Brugada syndrome. Because of this, we propose that β2-subunits play critical roles the establishment or maintenance normal electric activity vivo.To understand pathophysiological β2 heart, investigated phenotype Scn2b null mice. We observed reduced potassium current densities ventricular myocytes, as well conduction slowing right outflow...
Background: The mechanisms underlying spontaneous atrial fibrillation (AF) associated with ischemia/infarction are incompletely elucidated. Here, we investigate the AF in an ovine model of left myocardial infarction (LAMI). Methods and Results: LAMI was created by ligating branch anterior descending coronary artery. ECG loop recorders were implanted to monitor episodes. In 7 sheep, dantrolene—a ryanodine receptor blocker—was administered vivo during 8-day observation period (LAMI-D, 2.5...
Loss-of-function (LOF) variants in SCN1B, encoding the voltage-gated sodium channel β1/β1B subunits, are linked to neurological and cardiovascular diseases. Scn1b-null mice have spontaneous seizures ventricular arrhythmias die by approximately 21 days after birth. Subunits play critical roles regulating excitability of cardiomyocytes maintaining rhythmicity. However, whether they also regulate atrial is unknown. We used neonatal model effects SCN1B LOF on physiology pediatric patients. Scn1b...
On the basis of its ability to inhibit fibrosis, pirfenidone has drawn attention as an intriguing candidate for treating cardiac disease. However, precise electrophysiological effects have yet be elucidated. Here, we investigated potential modulate ion channels. Adult rat myocytes were using whole-cell patch-clamp, western-blot and qRT-PCR techniques. Pirfenidone increased density L-type Ca2+ current (ICaL, 50–100%), without significantly altering Na+, K+, or T-type currents. The effect was...
We investigated modulation of excitation-contraction (EC) coupling by calcitonin gene-related peptide (CGRP), which is released motorneurons during neuromuscular transmission. Mouse skeletal myotubes were cultured either under control conditions or in the presence 100 nm CGRP ( approximately 4-72 h). T- and L-type Ca(2+) currents, immobilization resistant charge movement, intracellular transients characterized whole-cell patch-clamp experiments. treatment increased amplitude voltage-gated...
Non‐Technical Summary Central core disease (CCD) is linked to mutations in the skeletal muscle ryanodine receptor (RyR1) gene that are believed disrupt excitation–contraction (EC) coupling. EC coupling requires activation of RyR1s release Ca 2+ from sarcoplasmic reticulum (SR). Subsequently, SR ‐ATPase (SERCA) returns cytoplasmic intracellular stores. Here, we have investigated effects two CCD RyR1 mutants (I4897T and Y523S) C2C12 myotubes. Both significantly altered myogenesis SERCA...
Chromatin in cervical cancer (CC) undergoes chemical and structural changes that alter the expression pattern of genes.Recently, a potential mechanism, which regulates gene at transcriptional levels is proteolytic clipping histone H3.However, until now this process CC has not been reported.Using HeLa cells as model human samples from patients with CC, we identify H3 cleavage was lower compared control tissue.Additionally, performed by serine aspartyl proteases cells.These results suggest...
Introduction: Recently we demonstrated that inhibition of the pro-fibrotic protein Galectin-3 reduces atrial dilatation, fibrosis and electrical remodeling as well fibrillation (AF) burden in a clinically relevant sheep model lone persistent AF (Takemoto Y, et al. Heart Rhythm 12:S4; 2015). The mineralocorticoid blocker eplerenone (EPL) has been shown to reduce incidence patients with systolic heart failure mild symptoms, but mechanism is poorly understood. We tested hypothesis by reducing...
Rationale: Aging is a strong risk factor for atrial fibrillation (AF), the most common sustained arrhythmia in clinical practice. Atrial inflammation correlates with increased AF susceptibility but whether chronic age-related that occurs atherosclerosis contributes to unknown. Hypothesis: Hematopoietic factors contribute inducibility aged atherosclerotic mice. Methods: We used burst electrical stimulation (tachypacing) of right atrium test in-vivo young and atherosclerotic, low density...
Introduction: Sudden Unexpected Death in Epilepsy (SUDEP) is a leading cause of death patients with epilepsy. While SUDEP mechanisms are not understood, there evidence to implicate autonomic dysfunction and cardiac arrhythmias. Loss-of-function variants SCN1A linked Dravet syndrome (DS). Importantly, expressed both heart brain humans rodents. Studies on Scn1a+/- DS mice induced pluripotent stem cell (iPSC)-derived myocytes from show altered electrophysiology that serves as substrates for...
Abstract During the different stages of cervical carcinogenesis there is an accumulation epigenetic alterations leading to changes in gene expression. High-risk human papillomavirus (hrHPV) a primary risk factor for cancer (CC). Impaired proteolytic processing histone H3 constitutes potential mechanism CC. However, whether this event occurs early HPV infection unknown. Using samples with normal pathology but positive and negative hrHPV, we identified that cleavage was low hrHPV cervix...