Transcriptional profiling of mouse heat left ventricle after dfferential cardiac remodeling in preload versus afterload.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Georgios Kararigas
PROVIDER: E-MEXP-2498 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
Differential cardiac remodeling in preload versus afterload.
Toischer Karl K Rokita Adam G AG Unsöld Bernhard B Zhu Wuqiang W Kararigas Georgios G Sossalla Samuel S Reuter Sean P SP Becker Alexander A Teucher Nils N Seidler Tim T Grebe Cornelia C Preuss Lena L Gupta Shamindra N SN Schmidt Kathie K Lehnart Stephan E SE Krüger Martina M Linke Wolfgang A WA Backs Johannes J Regitz-Zagrosek Vera V Schäfer Katrin K Field Loren J LJ Maier Lars S LS Hasenfuss Gerd G
Circulation 20100823 10
<h4>Background</h4>Hemodynamic load regulates myocardial function and gene expression. We tested the hypothesis that afterload and preload, despite similar average load, result in different phenotypes.<h4>Methods and results</h4>Afterload and preload were compared in mice with transverse aortic constriction (TAC) and aortocaval shunt (shunt). Compared with sham mice, 6 hours after surgery, systolic wall stress (afterload) was increased in TAC mice (+40%; P<0.05), diastolic wall stress (preload) ...[more]
Similar Datasets
Project description:: Heart failure is associated with high morbidity and mortality, and new therapeutic targets are needed. Preclinical data suggest that pharmacological activation of protein kinase G (PKG) can reduce maladaptive ventricular remodeling and cardiac dysfunction in the stressed heart. However, clinical trial results have been mixed, and the effects of long-term PKG activation in the heart are unknown.
2023-07-20 | PXD022600 | Pride
Project description:Comparison of mouse left ventricular responses to oestrogen with control.
2014-04-10 | E-MEXP-3834 | biostudies-arrayexpress
Project description:Heart failure is a leading cause of cardiovascular mortality with limited options for treatment. We analyzed whether the anti-ischemic drug ranolazine could retard the progression of heart failure in an experimental model of heart failure induced by 6 months of chronic pressure overload. The study showed that 2 months of ranolazine treatment improved cardiac function of aortic constricted C57BL/6J (B6) mice with symptoms of heart failure as assessed by echocardiography. The microarray gene expression study of heart tissue from failing hearts relative to ranolazine-treated and healthy control hearts identified heart failure-specific genes that were normalized during treatment with the anti-ischemic drug ranolazine. Microarray gene expression profiling was performed with heart tissue isolated from three study groups: (i) untreated 10 month-old C57BL/6J (B6) mice with heart failure induced by 6 months of abdominal aortic constriction (AAC), (ii) 10 month-old B6 mice with 6 months of AAC and two months of treatment with the anti-ischemic drug ranolazine (200 mg/kg), and (iii) age-matched, untreated, sham-operated B6 control mice.
2010-12-03 | E-GEOD-25766 | biostudies-arrayexpress
Project description:Diets influence metabolism and susceptibility to disease. We have previously demonstrated that a ketogenic diet alleviates cardiac pathology, with its cardioprotective effects linked to increased lysine acetylation in the heart. To identify acetylated proteins associated with this diet, we conducted a proteomic analysis using liquid chromatography-tandem mass spectrometry in the hearts of mice fed either a ketogenic diet or a normal chow diet under hypertension. We identified 966 acetylated peptides corresponding to 320 acetylated proteins in the hearts of mice fed a normal chow diet (group A), while 1597 acetylated peptides corresponding to 425 acetylated proteins were identified in the hearts of mice fed a ketogenic diet (group M).
2025-11-03 | PXD059855 | Pride
Project description:Cardiomyocyte-specific double knockout (DKO) mice lacking the catalytic domains of Dnmt3a (exon 18) and Dnmt3b (exon 19) were obtained by mating Dnmt3aflox and Dnmt3bflox mice [PMID 15757890] with mice expressing a cre recombinase under control of the cardiac atrial myosin light chain promoter (Myl7) [11689889]. Mice with the genotype Dnmt3aflox/flox, Dnmt3bflox/flox without expressing cre recombinase were used as control mice (CTL). Transcriptome analyses identified upregulation of 44 and downregulation of 9 genes in DKO as compared with control sham mice. TAC mice showed similar changes with substantial overlap of regulated genes compared to sham. Cardiac tissue from sham CTL (n=4) and DKO mice (n=4) as well as TAC-operated CTL (n=6) and DKO mice (n=6) was analysed.
2015-06-30 | E-GEOD-68518 | biostudies-arrayexpress
Project description:Background & Aims Obesity is a major risk factor for metabolic associated steatotic liver disease (MASLD) which can progress from metabolic associated steatotic liver (MASL) to metabolic associated steatohepatitis (MASH). There are currently no effective and validated screening tools to stratify obese patients with a greater risk for MASH, independent of liver fibrosis, at a population level. We aimed to characterise the highly abundant and small protein plasma proteomes of worsening MASLD and overlay the liver-secreted proteome to generate a predictive model to stratify patients with and without MASH. Methods Venous blood and liver wedge biopsies were taken from 160 patients undergoing bariatric surgery. MASLD severity was assessed histologically. Liver biopsies from a subset of 96 patients were precision-cut and cultured to assess liver-secreted proteins. Proteomic analysis was performed using liquid chromatography-tandem mass spectrometry on the plasma and the incubation medium cutoff the liver slices. Results Current non-invasive scores failed to stratify MASH in our cohort. The top200 plasma proteome exhibited mild changes in patients with MASH compared to those with No pathology, while the SPEA approach identified substantial differences in plasma proteins of patients with MASH compared to those without MASH. Liver-secreted proteins were remodelled in MASH compared to MASL and individuals with No pathology. There were no significant changes in the liver-secreted proteins and plasma proteome when comparing MASL to those with No pathology. The APASHA model, comprised of APOF, PCSK9, AFM, and S100A6, HbA1c % and AZGP1 stratified MASH in the discovery (AUROC: 0.887, p<0.0001) and validation cohorts (AUROC:0.7673, p=0.0002) and outcompeted other non-invasive scores. Conclusions These proteomic investigations provide a detailed description of liver-secreted and plasma proteome with worsening MASLD. MASH remodels plasma and liver-secreted proteins. Plasma proteomics generated the APASHA model validated in two Australian bariatric cohorts. Further investigation is warranted to interrogate the utility of the APASHA model as a non-invasive risk prediction model in additional cohorts. Lay Summary: Metabolic-associated steatohepatitis (MASH), a more advanced form of metabolic-associated steatotic liver disease (MASLD), alters the levels of many proteins secreted by the liver and in the blood and those. The APASHA model, which is based on proteins that change in the blood or are secreted by the liver in cases of MASH, could potentially be developed into a simple blood test to predict MASH in high-risk groups.
2025-04-14 | PXD052784 | Pride
Project description:Atherosclerosis and pressure overload are major risk factors for the development of heart failure in patients. Cardiac hypertrophy often precedes the development of heart failure. However, underlying mechanisms are incompletely understood. To investigate pathomechanisms underlying the transition from cardiac hypertrophy to heart failure we used experimental models of atherosclerosis- and pressure overload-induced cardiac hypertrophy and failure, i.e. apolipoprotein E (apoE)-deficient mice, which develop heart failure at an age of 18 months, and non-transgenic C57BL/6J (B6) mice with heart failure triggered by 6 months of pressure overload induced by abdominal aortic constriction (AAC). The development of heart failure was monitored by echocardiography, invasive hemodynamics and histology. The microarray gene expression study of cardiac genes was performed with heart tissue from failing hearts relative to hypertrophic and healthy heart tissue, respectively. The microarray study revealed that the onset of heart failure was accompanied by a strong up-regulation of cardiac lipid metabolism genes involved in fat synthesis, storage and oxidation. Microarray gene expression profiling was performed with heart tissue isolated from (i) 18 month-old apoE-deficient mice relative to age-matched non-transgenic C57BL/6J (B6) mice, (ii) 6 month-old apoE-deficient mice with 2 months of chronic pressure overload induced by abdominal aortic constriction (AAC) relative to sham-operated apoE-deficient mice and nontransgenic B6 mice, (iii) 10 month-old B6 mice with 6 months of AAC relative to sham-operated B6 mice, and (iv) 5 month-old B6 mice with 1 month of AAC relative to age-matched B6 mice.
2010-12-03 | E-GEOD-25765 | biostudies-arrayexpress
Project description:To verify the hypothesis that there are distinct subsets of cardiac fibroblasts, we performed single-cell RNA sequencing analysis of cardiac fibroblasts from pressure-overloaded ventricles.
2021-09-22 | E-MTAB-9839 | biostudies-arrayexpress
Project description:Heart failure is a leading cause of cardiovascular mortality with limited options for treatment. We used 18 month-old apolipoprotein E (apoE)- deficient mice as a model of atherosclerosis-induced heart failure to analyze whether the anti-ischemic drug ranolazine could retard the progression of heart failure. The study showed that 2 months of ranolazine treatment improved cardiac function of 18 month-old apoE-deficient mice with symptoms of heart failure as assessed by echocardiography. To identify changes in cardiac gene expression induced by treatment with ranolazine a microarray study was performed with heart tissue from failing hearts relative to ranolazine-treated and healthy control hearts. The microarray approach identified heart failure-specific genes that were normalized during treatment with the anti-ischemic drug ranolazine. Microarray gene expression profiling was performed with heart tissue isolated from (i) untreated 18 month-old apoE-deficient mice with heart failure relative to (ii) 18 month-old apoE-deficient mice treated for two months with the anti-ischemic drug ranolazine (200 mg/kg), and (iii) age-matched non-transgenic C57BL/6J (B6) control mice.
2010-12-03 | E-GEOD-25767 | biostudies-arrayexpress
Project description:Background: Fasciola hepatica infection still remains one of the helminthic neglected tropical diseases (NTDs). It has a huge worldwide distribution, affecting mainly cattle and, sometimes, human beings. In addition to data reported about the immunological response induced by helminthic infections and that induced by Fasciola hepatica, little is known about the gene expression profile in its organ target, the liver, which is where adult worms are established and live for long periods of time, causing its characteristic pathology. In the present work, we study both the early and late gene expression profiles in the livers of mice infected with Fasciola hepatica metacercariae using a microarray-based methodology. Methodology: A total of 9 female-6-week-old BALB/c mice (Charles River Laboratories, Barcelona, Spain) weighing 20 to 35 g were used for the experiments. Two groups of BALB/c mice were orally infected with seven F. hepatica metacercariae, and the other group remained untreated and served as a control. Mice were humanely euthanized and necropsied for liver recovery, histological assessment of hepatic damage, RNA isolation, microarray design and gene expression analysis on the day of infection (t0), seven days post-infection (t7) and twenty-one days post-infection (t21). Results: We found that Fasciola hepatica infection induces the differential expression of 128 genes in the liver in the early stage of infection and 308 genes in the late stage, and most of them are up-regulated. The Ingenuity Pathway Analysis revealed significant changes in the pathways related to metabolism, biosynthesis and signaling as well as genes implicated in inducing liver-toxicity, injury and death. Conclusion: The present study provides us insights at the molecular level about the underlying mechanisms used by Fasciola hepatica, leading to liver damage and its subsequent pathophysiology. The expression pattern obtained here could also be used to explain the lack of association between infection with F. hepatica and cholangiocarcinoma. However, more studies should be performed to confirm this hypothesis. We used three experimental groups each containing 3 mice. Group 1 remains untreated and served as control. Group 2 was infected with Fasciola hepatica metacercariae on day 0 and humanely necropsied at 7 days post-infection. Group 3 was infected with Fasciola hepatica metacercariae on day 0 and humanely necropsied at 21 days post- infection. At the time of necropsy, liver of each mice were removed and the RNA was isolated. We compared the gene expression profile in the liver of mice infected with Fasciola hepatica.
2015-06-05 | E-GEOD-69588 | biostudies-arrayexpress