Publications by authors named "Dor Yadin"
Article Synopsis
- Danon disease is a rare genetic disorder caused by LAMP2 mutations, primarily affecting heart function, leading to significant morbidity and mortality.
- In mouse models, treatment with RAAS inhibitors like Ramipril and Spironolactone showed effectiveness in reducing heart enlargement and improving function, while Angiotensin II worsened heart conditions.
- Gene therapy with AAV9-LAMP2 decreased harmful autophagosome buildup and oxidative stress, suggesting potential therapeutic options for managing Danon's cardiomyopathy in humans.
Danon disease is a lethal X-linked genetic syndrome resulting from radical mutations in the LAMP2 gene. LAMP2 protein deficiency results in defective lysosomal function, autophagy arrest and a multisystem disorder primarily involving the heart, skeletal muscle and the central nervous system. Cardiomyopathy is the main cause of morbidity and mortality.
View Article and Find Full Text PDFBackground Human mutations in the X-linked lysosome-associated membrane protein-2 () gene can cause a multisystem Danon disease or a primary cardiomyopathy characterized by massive hypertrophy, conduction system abnormalities, and malignant ventricular arrhythmias. We introduced an mutation (denoted L2) causing human cardiomyopathy, into mouse gene, to elucidate its consequences on cardiomyocyte biology. This mutation results in deletion of 41 amino acids, compatible with presence of some defective LAMP2 protein.
View Article and Find Full Text PDFCatecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited, stressed-provoked ventricular arrhythmia. CPVT is treated by β-adrenergic receptor blockers, Na channel inhibitors, sympathetic denervation, or by implanting a defibrillator. We showed recently that blockers of SK4 Ca-activated K channels depolarize the maximal diastolic potential, reduce the heart rate, and attenuate ventricular arrhythmias in CPVT.
View Article and Find Full Text PDFArticle Synopsis
- The published article contained errors in Table 1 due to issues during production.
- The specific errors involved incorrect values for FS and Body Weight in two different columns.
- The article has been updated to correct these errors and provide accurate information.
Article Synopsis
- Metabolic disorders like obesity and type 2 diabetes can lead to diabetic cardiomyopathy, characterized by heart muscle growth, mitochondrial dysfunction, and fibrosis influenced by angiotensin.
- In a study with diabetic mice, caloric restriction (CR) was shown to protect the heart against damage by reducing oxidative stress and inflammation, resulting in better cardiac health.
- The research found that CR preserved SIRT1 and PGC-1α activity, which are important for cellular defense, while inhibiting SIRT1 in heart cells decreased their protective effects, highlighting the role of these pathways in heart disease prevention.
Background: The recessive form of catecholaminergic polymorphic ventricular tachycardia 2 (CPVT2) is caused by mutations in cardiac calsequestrin (CASQ2), leading to protein deficiency.
Objectives: The aims of this study were to develop a viral-delivered gene therapy for CPVT2 and to determine the relationship between CASQ2 expression and antiarrhythmic efficacy in a murine model.
Methods: We used a murine model of CPVT2 caused by the D307H human mutation (CASQ2) or CASQ2 knockout (CASQ2).
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a stress-provoked ventricular arrhythmia, which also manifests sinoatrial node (SAN) dysfunction. We recently showed that SK4 calcium-activated potassium channels are important for automaticity of cardiomyocytes derived from human embryonic stem cells. Here SK4 channels were identified in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from healthy and CPVT2 patients bearing a mutation in calsequestrin 2 (CASQ2-D307H) and in SAN cells from WT and CASQ2-D307H knock-in (KI) mice.
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