Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA118759 | ENA |
REPOSITORIES: ENA
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Project description:Particulate Matter Triggers Carotid Body Dysfunction, Respiratory Dysynchrony and Cardiac Arrhythmias in Mice with Cardiac Failure; The mechanistic link between human exposure to airborne particulate matter (PM) pollution and the increased cardiovascular morbidity and mortality observed in people with congestive heart failure (CHF) is unknown. We now show that exposure of genetically-engineered mice with CHF (expressing a cardiac-specific CREB mutant transcription factor) to ambient PM (collected in Baltimore, mean aerodynamic diameter 1.9 um) unmasks severe autonomic morbidities manifested as significant reductions in heart rate variability, respiratory dysynchrony and increased frequency of serious ventricular arrhythmias, features not observed in PM-challenged wild type mice without CHF. PM exposure in CREB mice with CHF reflexly triggers autonomic dysfunction via heightened carotid body function as evidenced by pronounced afferent nerve responses to hypoxia and marked depression of breathing by hyperoxia challenge. Genomic analyses of lung and ventricular tissues revealed PM-induced molecular signatures of inflammation and oxidative stress. These findings in a murine model of cardiac failure provide the first direct assessment of autonomic function in response to PM challenge and are highly consistent with current epidemiologic findings on cardiovascular morbidity in susceptible PM-exposed human populations. We utilized a murine model of dilated cardiomyopathy to address potential mechanistic links between PM exposure and the development of life-threatening cardiac dysrhythmias. Experiment Overall Design: four group (n=3) of animals were treated by PBS or particulate matter (20mg/kg 1.9µm particulate matter) in Wild type or CD-1 dominate negative mice
2009-08-15 | E-GEOD-17478 | biostudies-arrayexpress
Project description:Particulate Matter Triggers Carotid Body Dysfunction, Respiratory Dysynchrony and Cardiac Arrhythmias in Mice with Cardiac Failure The mechanistic link between human exposure to airborne particulate matter (PM) pollution and the increased cardiovascular morbidity and mortality observed in people with congestive heart failure (CHF) is unknown. We now show that exposure of genetically-engineered mice with CHF (expressing a cardiac-specific CREB mutant transcription factor) to ambient PM (collected in Baltimore, mean aerodynamic diameter 1.9 um) unmasks severe autonomic morbidities manifested as significant reductions in heart rate variability, respiratory dysynchrony and increased frequency of serious ventricular arrhythmias, features not observed in PM-challenged wild type mice without CHF. PM exposure in CREB mice with CHF reflexly triggers autonomic dysfunction via heightened carotid body function as evidenced by pronounced afferent nerve responses to hypoxia and marked depression of breathing by hyperoxia challenge. Genomic analyses of lung and ventricular tissues revealed PM-induced molecular signatures of inflammation and oxidative stress. These findings in a murine model of cardiac failure provide the first direct assessment of autonomic function in response to PM challenge and are highly consistent with current epidemiologic findings on cardiovascular morbidity in susceptible PM-exposed human populations. We utilized a murine model of dilated cardiomyopathy to address potential mechanistic links between PM exposure and the development of life-threatening cardiac dysrhythmias.
2009-08-10 | GSE17478 | GEO
Project description:Developmental exposure to particulate matter air pollution is harmful to cardiovascular health, but the mechanisms by which this exposure mediates susceptibility to heart disease is poorly understood. We have previously shown, in a mouse model, that gestational exposure to diesel exhaust results in increased cardiac hypertrophy, fibrosis and susceptibility to heart failure in the adult offspring following transverse aortic constriction. In this study, we have analyzed gene expression in neonatal cardiomyocytes after gestational exposure by RNA-sequencing and have identified 300 genes that are dysregulated, including many involved in cardiac metabolism.
2019-04-17 | GSE110748 | GEO
Project description:Despite some success of pharmacotherapies targeting primarily neurohormonal dysregulation, heart failure is a growing global pandemic with increasing burden. Treatments that improve the disease by reversing heart failure at the cardiomyocyte level are lacking. MicroRNAs (miRNA) are transcriptional regulators of gene expression, acting through complex biological networks, and playing thereby essential roles in disease progression. Adverse structural remodelling of the left ventricle due to myocardial infarction (MI) is a common pathological feature leading to heart failure. We previously demonstrated increased cardiomyocyte expression of the miR-212/132 family during pathological cardiac conditions. Transgenic mice overexpressing the miR-212/132 cluster (miR-212/132-TG) develop pathological cardiac remodelling and die prematurely from progressive HF. Using both knockout and antisense strategies, we have shown miR-132 to be both necessary and sufficient to drive the pathological growth of cardiomyocytes in a murine model of left ventricular pressure overload. Based on the findings, we proposed that miR-132 may serve as a therapeutic target in heart failure therapy. Here we provide novel mechanistic insight and translational evidence for the therapeutic efficacy in small and large animal models (n=135) of heart failure. We demonstrate strong PK/PD relationship, dose-dependent efficacy and high clinical potential of a novel optimized synthetic locked nucleic acid phosphorothioate backbone antisense oligonucleotide inhibitor of miR-132 (antimiR-132) as a next-generation heart failure therapeutic.
2020-01-09 | PXD015337 | Pride
Project description:To evaluate the genome-wide changes in gene translational efficiency during the development of heart failure, we performed transverse aortic constriction(TAC) in male C57BL/6 mice. According to our experience, hypertrophy of the left ventricle was observed 2 weeks after TAC. Cardiac decompensation was observed at 5 weeks. We collected left ventricular tissues at 0, 2, 5 weeks after TAC and then performed ribosome footprinting and sequencing.
2023-10-31 | E-MTAB-8552 | biostudies-arrayexpress
Project description:Developmental exposure to particulate matter air pollution is harmful to cardiovascular health, but the mechanisms by which this exposure mediates susceptibility to heart disease is poorly understood. We have previously shown, in a mouse model, that gestational exposure to diesel exhaust results in increased cardiac hypertrophy, fibrosis and susceptibility to heart failure in the adult offspring following transverse aortic constriction. In this study we have found hypomethylation of DNA in neonatal cardiomyocytes isolated from in utero DE exposed neonates. We have demonstrated that in utero exposure to diesel exhaust alters the neonatal cardiomyocyte transcriptional and epigenetic landscapes, as well as the metabolic capability of these cells. Understanding how exposure alters the developing heart through dysregulation of gene expression, metabolism and DNA methylation is vital for identifying therapeutic interventions for air pollution-related heart failure.
2019-04-17 | GSE110792 | GEO
Project description:There is cardiac dysfunction in male eNOS (-/-) with age and 50% mortality at 21M. It was of interest to investigate the gene expression profile of aged eNOS (-/-) male in comparison to (+/+) in order to explore the genetic markers and molecular mechanisms leading to heart failure. RNA was extracted from the left ventricle from male (-/-) (n=3) and (+/+) (n=4) at the age of 21M.
2007-11-06 | E-GEOD-1988 | biostudies-arrayexpress
Project description:: The adult heart develops hypertrophy to reduce ventricular wall stress and maintain cardiac function in response to an increased workload. Although pathological hypertrophy generally progresses to heart failure, physiological hypertrophy may be cardioprotective. Cardiac-specific overexpression of the lipid-droplet protein perilipin 5 (Plin5) promotes cardiac hypertrophy, but it is unclear if this response is beneficial. We analyzed human RNA-sequencing data from the left ventricle and showed that cardiac PLIN5 expression correlates with upregulation of cardiac contraction-related processes. To investigate how elevated cardiac Plin5 levels affect cardiac contractility, we generated mice with cardiac-specific overexpression of Plin5 (MHC-Plin5 mice). These mice displayed increased left ventricular mass and cardiomyocyte size but preserved heart function. Quantitative proteomics identified sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2 (SERCA2) as a Plin5-interacting protein. Phosphorylation of phospholamban, the master regulator of SERCA2, was increased in MHC-Plin5 versus wild-type cardiomyocytes. Live imaging showed increases in intracellular Ca2+ release during contraction, Ca2+ removal during relaxation, and SERCA2 function in MHC-Plin5 versus wild-type cardiomyocytes. These results identify a role for Plin5 in improving cardiac contractility through enhanced Ca2+ signaling.
2023-01-20 | PXD035121 | Pride
Project description:Accumulation of activated cardiac fibroblasts plays a key role in heart failure progression. These cells deposit excessive extracellular matrix that leads to mechanical stiffness, myocyte uncoupling and ischemia. To investigate whether two developmentally distinct cardiac fibroblast populations exhibit distinct expression profiles in response to cardiac injury, and therefore might necessitate distinct therapeutic targeting, we performed microarray analysis on FACS sorted cells. Tie2cre lineage traced CFs, non Tie2cre lineage traced cardiac fibroblasts and endothelial cells were isolated from left ventricle of SHAM operated and banded hearts at the onset of fibrosis, one week after surgery. We used microarrays to detail the global programme of gene expression in cardiac fibroblasts and endothelium following pressure overload. Tie2cre lineage traced, non-tie2cre lineage traced fibroblasts and endothelial cells were sorted from left ventricle of 3 SHAM operated and 3 TAC operated adult male Black Swiss mice. Tie2cre lineage traced, non-tie2cre lineage traced fibroblasts and endothelial cells were sorted from left ventricle of 3 SHAM operated and 3 Transaortic Constriction (TAC) operated adult male Black Swiss mice for RNA extraction and Affymetrix microarray analysis. Hypertrophy in TAC animals, an lack of hypertrophy in SHAM operated animals, was evaluated by hemodynamic measurements before surgery and one week after surgery. Cells were isolated one week after surgery.
2014-05-19 | E-GEOD-45820 | biostudies-arrayexpress
Project description:Arterial pulmonary hypertension is a rare disease, with little knowledge regarding its etiology, and high mortality. Development of right and later on also left ventricular heart insufficiency, secondary to pulmonary hypertension, is a negative predictive factor. Genetic and molecular processes underlying left heart ventricle remodeling over the course of pulmonary hypertension remain unknown. In particular, there is no knowledge regarding the mechanisms of left heart ventricle atrophy which was completely avoided by researchers until recently.The aim of this study was to assess changes in protein abundance in left and right heart ventricle free wall of rats in monocrotaline model of PAH.
2020-09-07 | PXD015896 | Pride