A5087801799- Nuclear Structure and Function
- RNA Research and Splicing
- PARP inhibition in cancer therapy
- Atherosclerosis and Cardiovascular Diseases
- Phagocytosis and Immune Regulation
- Cell Adhesion Molecules Research
- Cancer, Lipids, and Metabolism
- Adipokines, Inflammation, and Metabolic Diseases
- Ubiquitin and proteasome pathways
- Immune cells in cancer
- Biomarkers in Disease Mechanisms
- Muscle Physiology and Disorders
- Erythrocyte Function and Pathophysiology
- Microtubule and mitosis dynamics
- Genetic Associations and Epidemiology
- Genomics and Chromatin Dynamics
- Genetics, Aging, and Longevity in Model Organisms
- Genital Health and Disease
- Endoplasmic Reticulum Stress and Disease
- Parvovirus B19 Infection Studies
- Immune Cell Function and Interaction
- Clusterin in disease pathology
- Cholesterol and Lipid Metabolism
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
Centro de Investigación en Red en Enfermedades Cardiovasculares
2018-2024
Spanish National Centre for Cardiovascular Research
2010-2024
Centro de Investigación Biomédica en Red
2018-2024
Instituto de Biomedicina de Valencia
2011
Consejo Superior de Investigaciones Científicas
2011
Kyushu University
2011
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,...
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...
Although tumor-associated macrophages (TAMs) are involved in tumor growth and metastasis, the mechanisms controlling their pro-tumoral activities remain largely unknown. The transcription factor c-MYC has been recently shown to regulate vitro human macrophage polarization be expressed infiltrating tumors. In this study, we exploited predominant expression of LysM myeloid cells generate c-Mycfl/fl LysMcre/+ mice, which lack c-Myc macrophages, investigate role cancer. Under steady-state...
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...
Cardiovascular disease (CVD) is the main cause of death worldwide, and aging its leading risk factor. Aging much accelerated in Hutchinson–Gilford progeria syndrome (HGPS), an ultra-rare genetic disorder provoked by ubiquitous expression a mutant protein called progerin. HGPS patients die their teens, primarily due to cardiovascular complications. The primary causes age-associated CVD are endothelial dysfunction dysregulated vascular tone; however, contribution progerin-induced remains...
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...
Background Atherosclerosis involves activation of the IRAK1/TRAF6/NF-κB inflammatory cascade, which is negatively regulated by miR146a. Previous studies showed that TT genotype rs2431697, located near miR-146a gene, drives lower transcription and predicts adverse cardiovascular events in anticoagulated atrial fibrillation patients. Moreover, systemic administration protects mice from atherosclerosis. Here we evaluated ability expression hematopoietic component to regulate atherosclerosis...
Genetic ablation of the growth suppressor p27(Kip1) (p27) in mouse aggravates atherosclerosis coinciding with enhanced arterial cell proliferation. However, it is unknown whether molecular mechanisms that limit p27's protective function contribute to development and p27 exerts proliferation-independent activities wall. This study aims provide insight into both questions by investigating role phosphorylation at serine 10 (p27-phospho-Ser10), a major posttranslational modification this...
Hutchinson-Gilford progeria syndrome (HGPS) is among the most devastating of laminopathies, rare genetic diseases caused by mutations in genes encoding nuclear lamina proteins. HGPS patients age prematurely and die adolescence, typically atherosclerosis-associated complications. The mechanisms HGPS-related atherosclerosis are not fully understood due to scarcity patient-derived samples availability only one atheroprone mouse model disease. Here, we generated a new atherosusceptible crossing...
Abstract Accumulation of lipid-laden macrophages within the arterial neointima is a critical step in atherosclerotic plaque formation. Here, we show that reduced levels cellular plasticity factor ZEB1 increase formation and chance cardiovascular events. Compared to control counterparts ( Zeb1 WT / Apoe KO ), male mice with ablation their myeloid cells ∆M ) have larger plaques higher lipid accumulation due delayed traffic deficient cholesterol efflux. display more pronounced systemic...
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...
Abstract Hutchinson‐Gilford progeria syndrome (HGPS) is a rare genetic disorder caused by mutation in the LMNA gene that provokes synthesis of progerin, mutant version nuclear protein lamin A accelerates aging and precipitates death. The most clinically relevant feature HGPS development cardiac anomalies severe vascular alterations, including massive loss smooth muscle cells, increased fibrosis, generalized atherosclerosis. However, it unclear if progerin expression endothelial cells (ECs)...
Abstract Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare genetic disease caused by expression of progerin, a lamin A variant that also expressed at low levels in non-HGPS individuals. Although HGPS patients die predominantly from myocardial infarction and stroke, the mechanisms provoke pathological alterations coronary cerebral arteries remain ill defined. Here, we assessed vascular function (CorAs) carotid (CarAs) progerin-expressing Lmna G609G/G609G mice (G609G), both...
Mutations in the LMNA gene (encoding lamin A/C proteins) cause several human cardiac diseases, including dilated cardiomyopathies (LMNA-DCM). The main clinical risks LMNA-DCM patients are sudden death and progressive left ventricular ejection fraction deterioration, therefore most animal studies have sought to define mechanisms through which mutations provoke alterations, with particular focus on cardiomyocytes. To investigate if also vascular alterations that might contribute...
Mutations in the LMNA gene (encoding lamin A/C proteins) cause several human cardiac diseases, including dilated cardiomyopathies (LMNA-DCM). The main clinical risks LMNA-DCM patients are sudden death and progressive left ventricular ejection fraction deterioration, therefore most animal studies have sought to define mechanisms through which mutations provoke alterations, with a particular focus on cardiomyocytes. To investigate if also vascular alterations that might contribute...
Familial partial lipodystrophy type 2 is an autosomal dominant disorder generally due to heterozygous missense variants in the LMNA gene.In women, phenotype begins manifest before puberty, while men onset later.It striking that most of cases reported literature are women.Specifically, our cohort only 27% these patients were men.Considering pattern inheritance disease where a similar ratio between males and females would be expected, it obvious majority with this do not they diagnosed.The...