A5070387528- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Cardiomyopathy and Myosin Studies
- Cardiac Fibrosis and Remodeling
- Ion Transport and Channel Regulation
- Muscle Physiology and Disorders
- Melanoma and MAPK Pathways
- RNA Research and Splicing
- Tissue Engineering and Regenerative Medicine
- Viral Infections and Immunology Research
- Cell Adhesion Molecules Research
- Eosinophilic Disorders and Syndromes
- Congenital heart defects research
- Clusterin in disease pathology
- Botanical Research and Chemistry
- Cardiac Arrhythmias and Treatments
- Kruppel-like factors research
- Sarcoidosis and Beryllium Toxicity Research
- Corneal surgery and disorders
- Prostate Cancer Diagnosis and Treatment
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Computational Drug Discovery Methods
- Cardiovascular Effects of Exercise
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
Spanish National Centre for Cardiovascular Research
2015-2024
Centro de Investigación en Red en Enfermedades Cardiovasculares
2022
Centro de Investigación Biomédica en Red
2022
Hospital de São João
2011-2015
Instituto de la Grasa
2014
Mount Sinai Hospital
2014
Icahn School of Medicine at Mount Sinai
2014
Tecnológico Nacional de México
2011
Instituto Politécnico Nacional
2011
Universidade do Porto
2011
Objectives— Patients with mutations in the proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) gene have hypercholesterolemia and are at high risk of adverse cardiovascular events. We aimed to stably express pathological human D374Y gain-of-function mutant form DY adult wild-type mice generate a hyperlipidemic proatherogenic animal model, achieved single systemic injection adeno-associated virus (AAV). Approach Results— constructed an AAV-based vector support targeted transfer liver....
Short QT syndrome type 3 (SQTS3) is a rare arrhythmogenic disease caused by gain-of-function mutations in KCNJ2, the gene coding inward rectifier potassium channel Kir2.1. We used multidisciplinary approach and investigated mechanisms an in-vivo model of de-novo mutation Kir2.1E299V identified patient presenting extremely abbreviated interval paroxysmal atrial fibrillation.
Patients with cardiomyopathy of Duchenne Muscular Dystrophy (DMD) are at risk developing life-threatening arrhythmias, but the mechanisms unknown. We aimed to determine role ion channels controlling cardiac excitability in arrhythmias DMD patients.
Abstract N-methyl-2-pyrrolidone (NMP) is a versatile water-miscible polar aprotic solvent. It used as drug solubilizer and penetration enhancer in human animal, yet its bioactivity properties remain elusive. Here, we report that NMP bioactive anti-inflammatory compound well tolerated vivo, shows efficacy reducing disease mouse model of atherosclerosis. Mechanistically, increases the expression transcription factor Kruppel-like 2 (KLF2) . Monocytes endothelial cells treated with express...
Andersen-Tawil syndrome type 1 is a rare heritable disease caused by mutations in the gene coding strong inwardly rectifying K
Andersen-Tawil syndrome (ATS) is a rare inheritable disease associated with loss-of-function mutations in KCNJ2, the gene coding strong inward rectifier potassium channel Kir2.1, which forms an essential membrane protein controlling cardiac excitability. ATS usually marked by triad of periodic paralysis, life-threatening arrhythmias and dysmorphic features, but its expression variable not all patients phenotype linked to have known genetic alteration. The mechanisms underlying this...
Stress-activated p38 kinases control a plethora of functions, and their dysregulation has been linked to the development steatosis, obesity, immune disorders, cancer. Therefore, they have identified as potential targets for novel therapeutic strategies. There are four family members (p38α, p38β, p38γ, p38δ) that activated by MKK3 MKK6. Here, we demonstrate lack MKK6 reduces lifespan in mice. Longitudinal study cardiac function KO mice showed young develop hypertrophy which progresses...
Abstract B lymphoma Mo-MLV insertion region 1 (Bmi1) is a polycomb-family transcriptional factor critical for self-renewal in many adult stem cells and human neoplasia. We sought to identify microRNAs regulated by Bmi1 that could play role multipotent cardiac progenitor cell (CPC) decisions. found miR-300, poorly characterized microRNA mapping the Dlk1-Dio3 cluster, was positively CPCs. Forced expression of miR-300 CPCs promoted an improved stemness signature with significant increase Oct4...
Adult cardiac progenitor/stem cells (CPC/CSC) are multipotent resident populations involved in homeostasis and heart repair. Assisted by complementary RNAseq analysis, we defined the fraction of CPC proteome associable with specific functions comparison human bone marrow mesenchymal stem (MSC), reference population for cell therapy, dermal fibroblasts (HDF), as a distant reference. Label-free proteomic analysis identified 526 proteins expressed differentially CPC. iTRAQ confirmed...
Andersen-Tawil syndrome type 1 (ATS1) is associated with life-threatening arrhythmias of unknown mechanism. In this study, we generated and characterized a mouse model ATS1 carrying the trafficking-deficient mutant Kir2.1
The insulin-like growth factor Ea propeptide (IGF-1Ea) is a powerful enhancer of cardiac muscle and regeneration, also blocking age-related atrophy beneficial in multiple skeletal diseases. therapeutic potential IGF-1Ea compared with mature IGF-1 derives from its local action the area synthesis. We have developed an adeno-associated virus (AAV) vector for delivery to heart treat mice after myocardial infarction examine reparative effects production on left ventricular remodelling. A...
Andersen-Tawil Syndrome Type 1 (ATS1) is a rare heritable disease caused by mutations in the strong inwardly rectifying K
ABSTRACT Background Patients with atrial fibrillation (AF) exhibit a reduction in the ultrarapid outward potassium current ( I Kur ) conducted by K V 1.5 channels. Ion channels are closely modulated regulatory subunits, forming macromolecular complexes known as channelosomes. One such family is leucine-rich glioma-inactivated protein (Lgi1-4), which has been shown to interact 1, modifying their trafficking and/or biophysical properties neurons. However, expression and impact of these...
Abstract Background Flecainide and other class-Ic antiarrhythmic drugs (AADs) are widely used in Andersen-Tawil syndrome type 1 (ATS1) patients. However, might be proarrhythmic some cases. We investigated the molecular mechanisms of class-I AADs proarrhythmia whether they increase risk death ATS1 patients with structurally normal hearts. Methods Results Of 53 reviewed from literature, 54% responded partially to flecainide, ventricular arrhythmia (VA) reduction only 23%. latter patients, VA...
Abstract Background Andersen-Tawil type 1 (ATS1) is associated with loss-of-function mutations in the inward rectifier potassium channel Kir2.1, which controls cardiac excitability and impulse conduction. Phosphatidylinositol-4,5-bisphosphate (PIP2) acts as an essential cofactor regulating opening of Kir2.1 channels. Fifty percent reported ATS1 affect Kir2.1-PIP2 interactions, leading to ECG defects, ventricular arrhythmias sudden death (SCD) by mechanisms that are poorly understood. Purpose...
ABSTRACT Andersen-Tawil Syndrome (ATS) is associated with life threatening arrhythmias of unknown mechanism. We report on a mouse model carrying the trafficking-deficient mutant Kir2.1 Δ314-315 . The recapitulates electrophysiological phenotype type 1 (ATS1), slower conduction velocities in response to flecainide, QT prolongation exacerbated by isoproterenol, and increased vulnerability calcium-mediated resembling catecholaminergic polymorphic ventricular tachycardia (CPVT). expression...