A5042332162- Autophagy in Disease and Therapy
- Congenital heart defects research
- Pluripotent Stem Cells Research
- Cardiomyopathy and Myosin Studies
- Cardiac electrophysiology and arrhythmias
- Muscle Physiology and Disorders
- Cardiovascular Effects of Exercise
- CRISPR and Genetic Engineering
- Cardiac Fibrosis and Remodeling
- Inflammasome and immune disorders
- Erythropoietin and Anemia Treatment
- Adipokines, Inflammation, and Metabolic Diseases
- Iron Metabolism and Disorders
- Cardiovascular Function and Risk Factors
- Acute Kidney Injury Research
- Adipose Tissue and Metabolism
- Extracellular vesicles in disease
- Neuroscience and Neural Engineering
- RNA Interference and Gene Delivery
- Effects of Radiation Exposure
- Amoebic Infections and Treatments
- Multilevel Inverters and Converters
- Tryptophan and brain disorders
- Alcohol Consumption and Health Effects
- Atherosclerosis and Cardiovascular Diseases
Stanford University
2020-2025
Cardiovascular Institute of the South
2020-2025
York University
2015-2024
Background: Although empagliflozin was shown to profoundly reduce cardiovascular events in diabetic patients and blunt the decline cardiac function nondiabetic mice with established heart failure (HF), mechanism of action remains unknown. Methods Results: We treated 2 rodent models HF 10 mg/kg per day measured activation NLRP3 (nucleotide-binding domain-like receptor protein 3) inflammasome heart. show for first time that beneficial effects reduced ejection fraction (HF [HFrEF]; n=30–34)...
The common aldehyde dehydrogenase 2 ( ALDH2 ) alcohol flushing variant known as ALDH2*2 affects ∼8% of the world’s population. Even in heterozygous carriers, this missense leads to a severe loss enzymatic activity and has been linked an increased risk coronary artery disease (CAD). Endothelial cell (EC) dysfunction plays determining role all stages CAD pathogenesis, including early-onset CAD. However, contribution EC its relation are not fully understood. In large genome-wide association...
Abstract Iron overload is associated with various pathological changes which contribute to heart failure. Here, we examined mechanisms via iron alters cardiomyocyte insulin sensitivity. Treatment of primary adult and neonatal cardiomyocytes as well H9c2 cells decreased sensitivity determined Western blotting or immunofluorescent detection Akt p70S6K phosphorylation glucose uptake. Using CellROX deep red DCF-DA probes also observed that increased generation reactive oxygen species (ROS),...
Lipocalin‐2 (Lcn2; also termed neutrophil gelatinase‐associated lipocalin (NGAL)) levels correlate positively with heart failure (HF) yet mechanisms via which Lcn2 contributes to the pathogenesis of HF remain unclear. In this study, we used coronary artery ligation surgery induce ischemia in wild‐type (wt) mice and induced a significant increase myocardial Lcn2. We then compared wt knockout (KO) observed that showed greater ischemia‐induced caspase‐3 activation DNA damage measured by TUNEL...
Abstract Strategies to enhance autophagy flux have been suggested improve outcomes in cardiac ischemic models. We explored the role of adiponectin mediating under conditions induced by permanent coronary artery ligation. studied molecular mechanisms underlying adiponectin's cardio‐protective effects knockout (Ad‐KO) compared with wild‐type (WT) mice subjected ischemia ligation and H9c2 cardiomyocyte cell line exposed hypoxia. Systemic infusion a cathepsin‐B activatable near‐infrared probe as...
Determining the pathogenicity of hypertrophic cardiomyopathy–associated mutations in β-myosin heavy chain ( MYH7 ) can be challenging due to its variable penetrance and clinical severity. This study investigates early pathogenic effects incomplete-penetrant G256E mutation on myosin function that may trigger adaptations hypertrophy. We hypothesized would alter biomechanical function, leading changes cellular functions. developed a collaborative pipeline characterize across protein, myofibril,...
<title>Abstract</title> Friedreich's ataxia (FA) is a mitochondrial disease caused by frataxin deficiency, leading to neurodegeneration and cardiomyopathy. Currently, there are no effective therapies for FA. Our study investigated the potential of myeloid cell replacement using bone marrow-derived cells in YG8-800 mouse model. Combining Busulfan myeloablation, Colony-stimulating factor 1 receptor inhibition, marrow transplantation, we achieved almost complete microglia tissue macrophage...
Heart failure is a leading cause of death, especially in the elderly or obese and diabetic populations. Various remodeling events have been characterized, which collectively contribute to progression heart failure. Of particular interest, autophagy has recently emerged as an important determinant cardiac function. Here, we used aged, 13-month-old, male adiponectin knockout (Ad-KO) wild-type (wt) mice subjected aortic banding induce pressure overload (PO). Cardiac strain analysis using...
Recent studies have shown that extracellular vesicles (EVs) secreted by various parasites are capable of modulating the host’s innate immune responses, such as altering macrophage (M ϕ ) phenotypes and functions. Studies M promote early host responses to amoebic infection releasing proinflammatory cytokines crucial combating amoebiasis. Here, we reporting for first time effect EVs released Entamoeba histolytica ( Eh EVs) on human THP‐1 differentiated (THP‐1 ). We show internalized which...
Hypertrophic cardiomyopathy (HCM) is an inherited cardiac disorder characterized by a thick left ventricular wall and increased risk of arrhythmias, heart failure, sudden death. The MYBPC3 PRAKG2 are known causal genes for HCM. Here we generated two human-induced pluripotent stem cell lines from HCM patients carrying heterozygous mutations in (c.459delC) PRKAG2 (c.1703C > T). Both iPSC expressed markers, had normal karyotype, were able to differentiate into three germ layers, making them...
Hypertrophic cardiomyopathy (HCM) is an inherited heart disease that can cause sudden cardiac death and failure. HCM often arises from mutations in sarcomeric genes, among which the MYBPC3 most frequently mutated. Here we generated two human induced pluripotent stem cell (iPSC) lines a patient who has familial history of his daughter carries pathogenic non-coding mutation. All show typical morphology cells, high expression pluripotency markers, normal karyotype, vitro capacity to...
Congenital long QT syndrome type 2 (LQT2) results from KCNH2 mutations that cause loss of Kv11.1 channel function which can lead to arrhythmias, syncope, and sudden death. Here, we generated three human-induced pluripotent stem cell (iPSC) lines peripheral blood mononuclear cells (PBMCs) two LQT2 patients carrying pathogenic variants (c.1714G > A c.2960del) one patient a variant uncertain significance (c.1870A T) in KCNH2. All show typical iPSC morphology, high expression markers, normal...
MYH7 heterozygous mutations are common genetic causes of hypertrophic cardiomyopathy (HCM). HCM is characterized by hypertrophy the left ventricle and diastolic dysfunction. We generated three human induced pluripotent stem cell (iPSC) lines from patients each carrying a single mutation in MYH7, c.2167C > T, c.4066G A, c.5135G respectively. All expressed high levels markers, had normal karyotype, possessed capability differentiation into derivatives germ layers, which can serve as valuable...
Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited heart disease which can cause life-threatening arrhythmias and cardiac dysfunction. The autosomal dominant form of ARVD/C caused by mutations in the desmosome, such as those plakoglobin plakophilin-2 (PKP2) gene. Here, we generated three human induced pluripotent stem cell (iPSC) lines from peripheral blood mononuclear cells (PBMCs) patients carrying pathogenic variants their PKP2 genes (c.2065_2070delinsG;...
Long QT Syndrome (LQTS) is a genetic heart disorder that can induce cardiac arrhythmias. The most prevalent subtype, LQT1, stems from rare variants in the KCNQ1 gene. Utilizing induced pluripotent stem cells (iPSCs) enables detailed cellular studies and personalized medicine approaches for this life-threatening condition. We generated two LQT1 iPSC lines with single nucleotide nonsense mutations, c.1031 C > T c.1121 A KCNQ1. Both exhibited typical morphology, expressed high levels of...