A5084297640- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Cardiomyopathy and Myosin Studies
- RNA Research and Splicing
- Muscle Physiology and Disorders
- PARP inhibition in cancer therapy
- Nuclear Structure and Function
- Ion Transport and Channel Regulation
- Sphingolipid Metabolism and Signaling
- Eicosanoids and Hypertension Pharmacology
- Immune Response and Inflammation
- Receptor Mechanisms and Signaling
- Lipid Membrane Structure and Behavior
- Cardiac Arrhythmias and Treatments
- Neuroscience and Neuropharmacology Research
- Asthma and respiratory diseases
- Adipose Tissue and Metabolism
- Adenosine and Purinergic Signaling
- Viral Infectious Diseases and Gene Expression in Insects
- Plant-based Medicinal Research
- Atherosclerosis and Cardiovascular Diseases
- Pulmonary Hypertension Research and Treatments
- Genetics, Aging, and Longevity in Model Organisms
- Cell Adhesion Molecules Research
- Analytical Methods in Pharmaceuticals
Spanish National Centre for Cardiovascular Research
2019-2024
Centro de Investigación en Red en Enfermedades Cardiovasculares
2020-2022
Centro de Investigación Biomédica en Red
2020-2022
Instituto de Investigaciones Biomédicas Sols-Morreale
2010-2021
Universidad Autónoma de Madrid
2010-2021
Consejo Superior de Investigaciones Científicas
2011-2014
Abstract Aims The aim of this study was to changes in coronary microcirculation status during and after several cycles anthracycline treatment. Methods results Large-white male pigs (n=40) were included different experimental protocols (ExPr.) according cumulative exposure [0.45 mg/kg intracoronary (IC) doxorubicin per injection] follow-up: control (no doxorubicin); single injection sacrifice either at 48 h (ExPr. 1) or 2 weeks 2); 3 injections apart (low dose) 3) 12 4) third injection; five...
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.
Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare genetic disorder for which no cure exists. The disease characterized by premature aging and inevitable death in adolescence due to cardiovascular complications. Most HGPS patients carry a heterozygous de novo LMNA c.1824C > T mutation, provokes the expression of dominant-negative mutant protein called progerin. Therapies proven effective HGPS-like mouse models have yielded only modest benefit clinical trials. To overcome gap...
Background: Hutchinson-Gilford progeria syndrome (HGPS) is a rare disorder characterized by premature aging and death mainly because of myocardial infarction, stroke, or heart failure. The disease provoked progerin, variant lamin A expressed in most differentiated cells. Patients look healthy at birth, symptoms typically emerge the first second year life. Assessing reversibility progerin-induced damage relative contribution specific cell types critical to determining potential benefits late...
Dietary n-3 polyunsaturated fatty acids (PUFAs) have been reported to exhibit antiarrhythmic properties, and these effects attributed their capability modulate ion channels. In the present review, we will focus on of PUFAs a cardiac sodium channel (Na(v)1.5) two potassium channels involved in atrial ventricular repolarization (K(v)) (K(v)1.5 K(v)11.1). marine (docosahexaenoic, DHA eicosapentaenoic acid, EPA) plant origin (alpha-linolenic ALA) block K(v)1.5 K(v)11.1 at physiological...
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.
Potassium channels modulate macrophage physiology. Blockade of voltage-dependent potassium (Kv) by specific antagonists decreases cytokine production and inhibits proliferation. In the presence aspirin, acetylated cyclooxygenase-2 loses activity required to synthesize PGs but maintains oxygenase produce 15R-HETE from arachidonate. This intermediate product is transformed via 5-LOX into epimeric lipoxins, termed 15-epi-lipoxins (15-epi-lipoxin A4 [e-LXA4]). Kv have been proposed as...
Pulmonary hypertension (PH) can affect both pulmonary arterial tree and cardiac function, often leading to right heart failure death. Despite the urgency, lack of understanding has limited development effective therapeutic strategies. Our research reveals that MCJ modulates mitochondrial response chronic hypoxia. levels elevate under hypoxic conditions, as in lungs patients affected by COPD, mice exposed hypoxia, myocardium from pigs subjected ventricular (RV) overload. The absence preserves...
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...
Neutral sphingomyelinase (nSMase)-derived ceramide has been proposed as a mediator of hypoxic pulmonary vasoconstriction (HPV), specific response the circulation. Voltage-gated K(+) (K(v)) channels are modulated by numerous vasoactive factors, including hypoxia, and their inhibition involved in HPV. Herein, we have analyzed effects on K(v) currents contractility rat arteries (PA) mesenteric (MA). The analog C6-ceramide inhibited PA smooth muscle cells (PASMC). Similar were obtained after...
Irvalec is a marine-derived antitumor agent currently undergoing phase II clinical trials. In vitro, induces rapid loss of membrane integrity in tumor cells, accompanied significant Ca2+ influx, perturbations conductivity, severe swelling and the formation giant membranous vesicles. All these effects are not observed Irvalec-resistant or significantly delayed by pretreating cells with Zn2+. Using fluorescent derivatives it was demonstrated that compound rapidly interacts plasma promoting...
Abstract Aims Hutchinson–Gilford progeria syndrome (HGPS) is an ultrarare laminopathy caused by expression of progerin, a lamin A variant, also present at low levels in non-HGPS individuals. HGPS patients age and die prematurely, predominantly from cardiovascular complications. Progerin-induced cardiac repolarization defects have been described previously, although the underlying mechanisms are unknown. Methods results We conducted studies heart tissue progerin-expressing LmnaG609G/G609G...
Andersen-Tawil syndrome type 1 is a rare heritable disease caused by mutations in the gene coding strong inwardly rectifying K
Plasma membrane integrity is essential for cell life. Any major break on it immediately induces the death of affected cell. Different molecules were described as disrupting this structure and thus showing antitumor activity. We have previously defined that elisidepsin (Irvalec®, PM02734) inserts self-organizes in plasma tumor cells, inducing a rapid loss integrity, permeabilization necrotic death. Here we show that, sensitive HCT-116 colorectal all these effects are consequence interaction...
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
Polyunsaturated fatty acids (PUFAs) have been reported to exhibit antiarrhythmic properties, which are attributed their capability modulate ion channels. This PUFAs ability has be due effects on the gating properties of In present review, we will focus role two Kv channels, Kv1.5 and Kv11.1. channels blocked by n-3 marine [docosahexaenoic acid (DHA) eicosapentaenoic acid] plant origin (alpha-linolenic acid, ALA) at physiological concentrations. The blockade steeply increased in range...
Aging is the main risk factor for cardiovascular and metabolic diseases, which have become a global concern as world population ages. These diseases aging process are exacerbated in Hutchinson-Gilford progeria syndrome (HGPS or progeria). Here, we evaluated cardiometabolic disease animal models of premature normal with aim identifying alterations that shared specific to each condition. Despite differences body composition markers, prematurely normally mice developed heart failure similar...
Andersen-Tawil Syndrome Type 1 (ATS1) is a rare heritable disease caused by mutations in the strong inwardly rectifying K
The Kv β1.3 subunit modifies the gating and pharmacology of 1.5 channels in a PKC-dependent manner, decreasing channel sensitivity to bupivacaine- quinidine-mediated blockade. Cardiac associate with receptor for activated C kinase 1 (RACK1), different PKC isoforms, resulting formation functional channelosome. aim present study was investigate effects inhibition on bupivacaine quinidine block + channels.HEK293 cells were transfected channels, currents recorded using whole-cell configuration...
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...