Search results for "Type I"
showing 10 items of 966 documents
Systemic blockade of ACVR2B ligands attenuates muscle wasting in ischemic heart failure without compromising cardiac function
2020
Signaling through activin receptors regulates skeletal muscle mass and activin receptor 2B (ACVR2B) ligands are also suggested to participate in myocardial infarction (MI) pathology in the heart. In this study, we determined the effect of systemic blockade of ACVR2B ligands on cardiac function in experimental MI, and defined its efficacy to revert muscle wasting in ischemic heart failure (HF). Mice were treated with soluble ACVR2B decoy receptor (ACVR2B-Fc) to study its effect on post-MI cardiac remodeling and on later HF. Cardiac function was determined with echocardiography, and myocardium analyzed with histological and biochemical methods for hypertrophy and fibrosis. Pharmacological blo…
Lipoprotein-associated phospholipase A₂ activity is increased in patients with definite familial hypercholesterolemia compared with other forms of hy…
2018
International audience; Background and Aim: Lipoprotein-associated phospholipase A2 (Lp-PLA2) plays a key role in atherosclerosis development. It is considered a marker of increased risk of cardiovascular disease (CVD) and plaque vulnerability. Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated plasma levels of low-density lipoprotein cholesterol and a higher prevalence of early CVD. Our aim was to evaluate the differences in Lp-PLA2 activity in a population of hypercholesterolemic patients with and without definite FH.Methods and Results: Hypercholesterolemic patients were consecutively recruited. Definite FH was defined according to Dutch Lipid Clinic Netwo…
Sequential BMP7/TGF-β1 signaling and microbiota instruct mucosal Langerhans cell differentiation
2018
Capucha et al. demonstrate that mucosal Langerhans cell (LC) differentiation from pre–dendritic cells and monocytes involves consecutive BMP7 and TGF-β1 signaling in separate anatomical locations. Moreover, mucosal microbiota regulates the development of LCs that in turn shape microbial and immunological homeostasis.
Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy
2016
Lymphoid organs, in which antigen presenting cells (APCs) are in close proximity to T cells, are the ideal microenvironment for efficient priming and amplification of T-cell responses. However, the systemic delivery of vaccine antigens into dendritic cells (DCs) is hampered by various technical challenges. Here we show that DCs can be targeted precisely and effectively in vivo using intravenously administered RNA-lipoplexes (RNA-LPX) based on well-known lipid carriers by optimally adjusting net charge, without the need for functionalization of particles with molecular ligands. The LPX protects RNA from extracellular ribonucleases and mediates its efficient uptake and expression of the encod…
Homozygous Familial Hypercholesterolemia in Spain Prevalence and Phenotype-Genotype Relationship
2016
Background— Homozygous familial hypercholesterolemia (HoFH) is a rare disease characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) and extremely high risk of premature atherosclerotic cardiovascular disease. HoFH is caused by mutations in several genes, including LDL receptor ( LDLR ), apolipoprotein B ( APOB ), proprotein convertase subtilisin/kexin type 9 ( PCSK9 ), and LDL protein receptor adaptor 1 ( LDLRAP1 ). No epidemiological studies have assessed HoFH prevalence or the clinical and molecular characteristics of this condition. Here, we aimed to characterize HoFH in Spain. Methods and Results— Data were collected from the Spanish Dyslipidemia Regist…
Differential impact of high and low penetrance TNFRSF1A gene mutations on conventional and regulatory CD4+ T cell functions in TNFR1-associated perio…
2015
Abstract TNFR-associated periodic syndrome is an autoinflammatory disorder caused by autosomal-dominant mutations in TNFRSF1A, the gene encoding for TNFR superfamily 1A. The lack of knowledge in the field of TNFR-associated periodic syndrome biology is clear, particularly in the context of control of immune self-tolerance. We investigated how TNF-α/TNFR superfamily 1A signaling can affect T cell biology, focusing on conventional CD4+CD25− and regulatory CD4+CD25+ T cell functions in patients with TNFR-associated periodic syndrome carrying either high or low penetrance TNFRSF1A mutations. Specifically, we observed that in high penetrance TNFR-associated periodic syndrome, at the molecular le…
CD40L controls obesity-associated vascular inflammation, oxidative stress, and endothelial dysfunction in high fat diet-treated and db/db mice
2018
Abstract Aims CD40 ligand (CD40L) signaling controls vascular oxidative stress and related dysfunction in angiotensin-II-induced arterial hypertension by regulating vascular immune cell recruitment and platelet activation. Here we investigated the role of CD40L in experimental hyperlipidemia. Methods and results Male wild type and CD40L−/− mice (C57BL/6 background) were subjected to high fat diet for sixteen weeks. Weight, cholesterol, HDL, and LDL levels, endothelial function (isometric tension recording), oxidative stress (NADPH oxidase expression, dihydroethidium fluorescence) and inflammatory parameters (inducible nitric oxide synthase, interleukin-6 expression) were assessed. CD40L exp…
Lipidomic profiling identifies signatures of metabolic risk
2020
Background: Metabolic syndrome (MetS), the clustering of metabolic risk factors, is associated with cardiovascular disease risk. We sought to determine if dysregulation of the lipidome may contribute to metabolic risk factors. Methods: We measured 154 circulating lipid species in 658 participants from the Framingham Heart Study (FHS) using liquid chromatography-tandem mass spectrometry and tested for associations with obesity, dysglycemia, and dyslipidemia. Independent external validation was sought in three independent cohorts. Follow-up data from the FHS were used to test for lipid metabolites associated with longitudinal changes in metabolic risk factors. Results: Thirty-nine lipids were…
Blockade of the trans-sulfuration pathway in acute pancreatitis due to nitration of cystathionine β-synthase
2019
© 2019 Published by Elsevier B.V.
Neuronal nitric oxide synthase is involved in CB/TRPV1 signalling: Focus on control of hippocampal hyperexcitability
2017
Cannabinoids (CB), transient receptors potential vanilloid type 1 (TRPV1) and nitric oxide (NO) were found to be interlinked in regulating some neuronal functions such as membrane excitability and synaptic transmission. TRPV1 play a fundamental role since it represents a synaptic target for CB that triggers several downstream cellular pathways. In this regard, recent evidence report that TRPV1 could influence NO production by modulating neuronal NO synthase (nNOS) activity. In the present research, we pointed to manipulate nNOS function to assess its role on TRPV1 signalling in hyperexcitability conditions elicited in the dentate gyrus of hippocampal formation. The activation of TRPV1 recep…