A5069519361- Nuclear Structure and Function
- RNA Research and Splicing
- Protease and Inhibitor Mechanisms
- Peptidase Inhibition and Analysis
- Cell Adhesion Molecules Research
- PARP inhibition in cancer therapy
- Alzheimer's disease research and treatments
- Signaling Pathways in Disease
- Inflammatory Bowel Disease
- T-cell and B-cell Immunology
- Cardiac Fibrosis and Remodeling
- Blood Coagulation and Thrombosis Mechanisms
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Photographic and Visual Arts
- Microtubule and mitosis dynamics
- Neuroscience and Neuropharmacology Research
- Zebrafish Biomedical Research Applications
- Endoplasmic Reticulum Stress and Disease
- Pancreatic function and diabetes
- Media, Journalism, and Communication History
- Ubiquitin and proteasome pathways
- Liver physiology and pathology
- S100 Proteins and Annexins
- Cholinesterase and Neurodegenerative Diseases
Spanish National Centre for Cardiovascular Research
2008-2024
Centro de Investigación Biomédica en Red
2020-2024
Centro de Investigación en Red en Enfermedades Cardiovasculares
2020-2024
Universidad de Valladolid
2003-2010
University of Konstanz
2010
Instituto de Salud Carlos III
2001-2007
Centro Nacional de Microbiologia
2002-2007
Universidad Autónoma de Madrid
2001-2002
Consejo Superior de Investigaciones Científicas
2002
Centro de Biología Molecular Severo Ochoa
2001
Progerin, an aberrant protein that accumulates with age, causes the rare genetic disease Hutchinson-Gilford progeria syndrome (HGPS). Patients who have HGPS exhibit ubiquitous progerin expression, accelerated aging and atherosclerosis, die in their early teens, mainly of myocardial infarction or stroke. The mechanisms underlying progerin-induced atherosclerosis remain unexplored, part, because lack appropriate animal models.We generated atherosclerosis-prone model by crossing apolipoprotein...
Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder caused by progerin, mutant lamin A variant. HGPS patients display accelerated aging and die prematurely, typically from atherosclerosis complications. Recently, we demonstrated that progerin-driven vascular smooth muscle cell (VSMC) loss accelerates leading to premature death in apolipoprotein E-deficient mice. However, the molecular mechanism underlying this process remains unknown. Using transcriptomic approach,...
Dormant or slow-cycling tumor cells can form a residual chemoresistant reservoir responsible for relapse in patients, years after curative surgery and adjuvant therapy. We have adapted the pulse-chase expression of H2BeGFP labeling isolating cancer (SCCCs). SCCCs showed initiation potential enhanced chemoresistance. Cells at this status presented distinctive nongenetic cell-autonomous gene profile shared across different types. identified TET2 epigenetic enzyme as key factor controlling SCCC...
The retinoid X receptor α (RXRα) plays a central role in the regulation of many intracellular signaling pathways and can mediate ligand-dependent transcription by forming homodimers or heterodimers with other nuclear receptors. Although several members hormone superfamily have emerged as important regulators macrophage gene expression, existence vivo an RXR pathway macrophages has not been established. Here, we provide evidence that RXRα regulates chemokines Ccl6 Ccl9 independently...
Macrophages (Mφs) produce factors that participate in cardiac repair and remodeling after myocardial infarction (MI); however, how these crosstalk with other cell types mediating is not fully understood. Here we demonstrated Mφs increased the expression of Mmp14 (MT1-MMP) 7 days post-MI. We selectively inactivated gene using a genetic strategy ( f/f : Lyz2 -Cre). This conditional KO (MAC-Mmp14 KO) resulted attenuated post-MI dysfunction, reduced fibrosis, preserved capillary network....
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...
Article3 December 2019Open Access Source DataTransparent process Endothelial MT1-MMP targeting limits intussusceptive angiogenesis and colitis via TSP1/nitric oxide axis Sergio Esteban Vascular Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain Search for more papers by this author Cristina Clemente Biológicas (CIB-CSIC), Agnieszka Koziol Pilar Gonzalo Rius CIBER Enfermedades (CIBER-CV), Fernando Martínez Bioinformatics Unit, Pablo M Linares...
The vaccinia‐related kinase (VRK) proteins are a new group of three Ser‐Thr kinases in the human kinome. VRK upstream regulators several transcription factors. VRK1 phosphorylates p53 Thr‐18 within region binding to mdm2 preventing their interaction. tissue distribution genes is still largely unknown. In present report expression these was analyzed during murine hematopoietic development. expressed fetal liver and peripheral blood, with higher levels between days 11.5 13.5, time when there...
Hutchinson–Gilford progeria syndrome (HGPS, progeria) is a rare genetic disease characterized by premature aging and death in childhood for which there were no approved drugs its treatment until last November, when lonafarnib obtained long-sought FDA approval. However, the benefits of patients are limited, highlighting need new therapeutic strategies. Here, we validate enzyme isoprenylcysteine carboxylmethyltransferase (ICMT) as target with development series potent inhibitors this that...
Atherosclerosis is the main medical problem in Hutchinson-Gilford progeria syndrome, a rare premature aging disorder caused by mutant lamin-A protein progerin. Recently, we found that limiting progerin expression to vascular smooth muscle cells (VSMCs) sufficient hasten atherosclerosis and death
Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare disease caused by the expression of progerin, aberrant protein produced a point mutation in LMNA gene. HGPS patients show accelerated aging and die prematurely mainly from complications atherosclerosis such as myocardial infarction, heart failure, or stroke. However, mechanisms underlying vascular pathology remain ill defined. We used single-cell RNA sequencing to characterize aorta progerin-expressing LmnaG609G/G609G mice...
Embryo liver morphogenesis takes place after gastrulation and starts with a ventral foregut evagination that reacts to factor signaling from both cardiac mesoderm septum transversum mesenchyme. Current knowledge of the progenitor stem cell populations involved in this early embryo development is scarce. We describe here population 11-day postcoitus c-Kitlow(CD45/TER119)– progenitors selectively expressed hepatospecific genes proteins vivo, was self-maintained vitro by long-term...
The mechanism by which proteolytic events translate into biological responses is not well understood. To explore the link of pericellular proteolysis to relevant capillary sprouting within inflammatory context, we aimed at identification collection substrates protease MT1-MMP in endothelial tip cells induced stimuli. We applied quantitative proteomics (ECs) derived from wild-type and MT1-MMP-null mice identify substrate repertoire this TNF-α-activated ECs. Bioinformatics analysis revealed a...
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...
Hutchinson–Gilford progeria syndrome (HGPS) is a rare disease caused by the expression of progerin, mutant protein that accelerates aging and precipitates death. Given atherosclerosis complications are main cause death in progeria, here, we investigated whether progerin-induced prevented HGPSrev-Cdh5-CreERT2 HGPSrev-SM22α-Cre mice with progerin suppression endothelial cells (ECs) vascular smooth muscle (VSMCs), respectively. were undistinguishable from HGPSrev ubiquitous expression, contrast...