Project description:Heart failure is one of the leading causes of death in an ageing population. Hallmarks are cardiac hypertrophy, fibrosis and inflammation. The molecular mechanisms, however, are poorly understood. Glycosylation is one of the most common posttranslational modifications of proteins, which can have important consequences for protein folding, function and turnover. We hypothesized that changes in glycoprotein abundance and glycosylation patterns may contribute to cardiac aging. Western Blot analysis suggests increased protein mannosylation in the aging heart. Glycoprotein pull-downs from heart lysates of young (3 months) and old (2 years) mice in combination with quantitative mass spectrometry support widespread alterations of the glycoproteome in aged hearts.
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.
Project description:Redox proteomic data from the heart of young mice, old mice, or mice treated with SS31. Quantification of protein-S-glutathionylation was performed using an established redox proteomics workflow. LC-MS/MS raw data were searched with MS-GF+ against the mouse protein sequence database from the Uniprot.
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.
Project description:To investigate ageing-related changes in cardiac transcriptome of FVB mice we performed differential gene expression profiling analysis using data obtained from RNA-seq of five life time points (4-, 8-, 10-, 12-, 14 months) by comparing older FVB mice (8-, 10-, 12-, 14 months) to young 4-month-old FVB mice (FVB vs. FVB analysis). Genes that were differentially expressed in FVB vs. FVB analysis were also annotated to the respective biological processes based on Gene Ontology database, assessed for their overrepresentation to indicate processes involved in cardic ageing process in FVB mice. To investigate heart failure-related as well as ageing-related changes in cardiac transcriptome of Tgαq*44 mice we performed differential gene expression profiling analysis using data obtained from RNA-seq of five life time points (4-, 8-, 10-, 12-, 14 months) by comparing Tgαq*44 to age-matched FVB mice (Tgαq*44 vs. FVB analysis). Genes that were differentially expressed in Tgαq*44 vs. FVB analysis were also annotated to the respective biological processes based on Gene Ontology database, assessed for their overrepresentation to indicate processes iniciated along heart failure development as well as cardiac ageing process in Tgαq*44 mice. To investigate early activated ageing-related changes in cardiac transcriptome of Tgαq*44 mice during entire heart failure development we searched for the presence of ageing-related genes (those identified in cardiac transcriptome of older FVB mice) among genes which were differentially expressed commonly at each measured time points in Tgαq*44 vs. FVB analysis. To investigate early activated aging-related biological processes in cardiac transcriptome of Tgαq*44 mice during entire heart failure development, we searched for the presence of ageing-related processes (those identified in cardiac transcriptome of older FVB mice) among processes which were overrepresented commonly at each measured time points in Tgαq*44 vs. FVB analysis.
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.
Project description:To identify the gene expression change during pituitary aging, we did the RNA-seq of pituitary from 2-3 months young mice and 18-24 months old mice. The mRNA level of different genes were analyzed.
Project description:We performed gene expression profile of different B cell populations found in old (18 months old) C57BL/6 female mouse (B1 cells were recovered from both young and old C57BL/6 mice). Mice were naïve and healthy (no autoimmunity was detected at the time of the experiment).
Project description:Substantia nigra pars compacta (SNpc) is highly sensitive to normal aging and selectively degenerates in Parkinson's disease. Until now, molecular mechanisms behind SNpc aging have not been fully investigated using high throughput techniques. Here, aging-associated early changes in transcriptome of SNpc were investigated comparing late middle-aged (18 months old) to young (2 months old) mice. Three age groups of C57 wild type mice were used in microarray analysis: young (2 months old), middle aged (10 months old), and late-middle aged (18 months old) mice. Four replicates were included in each age group and each replicate was pooled from 4 mice (4 mice/replicate x 4 replicates x 3 age groups). Total RNA was isolated from SNpc for hybridization on Affymetrix microarrays.