Project description:Nuclear receptor Reverb alpha is a component of circadian rythm which could be evolved in cardioprotection strategy. We test if pharmacological modulation of these target could be suitable for cardioprotection after ischemia reperfusion injury We used microarrays to detail the global programme of gene expression
Project description:Nuclear receptor Reverb alpha is a component of circadian rythm which could be evolved in cardioprotection strategy. We test if pharmacological modulation of these target could be suitable for cardioprotection after ischemia reperfusion injury We used microarrays to detail the global programme of gene expression
Project description:Liver metabolism in mice lacking Bmal1 in adipocytes. Comparison between WT and KO revealed no differentially expressed genes at ZT12 and ZT16, and only revealed one gene at ZT8 and ZT20. In contrast many genes were differential at ZT0 and ZT4. With ZT4 having substantially more than ZT0.
Project description:Early reperfusion of ischemic cardiac tissue remains the most effective intervention for improving clinical outcome following myocardial infarction. However, abrupt increases in intracellular Ca2+ during myocardial reperfusion cause cardiomyocyte death and consequent loss of cardiac function, referred to as ischemia/reperfusion (IR) injury. Cardiac IR is accompanied by dynamic changes in expression of microRNAs (miRNAs), which inhibit specific mRNA targets. miR-214 is up-regulated during ischemic injury and heart failure in mice and humans, but its potential role in these processes is unknown. We show that genetic deletion of miR-214 in mice causes loss of cardiac contractility, increased apoptosis, and excessive fibrosis in response to IR injury. The microarray contains 6 samples, each containing cDNA pooled from 3 mice per group. There are no replicates. The array was designed to make 3 different pairwise comparisons between the following: P14 WT and miR-214 KO hearts; adult WT and miR-214 KO skeletal muscle; adult WT and miR-214 KO hearts
Project description:Heart disease remains the leading cause of death globally. Although reperfusion following myocardial ischemia can prevent death by restoring nutrient flow, ischemia/reperfusion injury can cause significant heart damage. The mechanisms that drive ischemia/reperfusion injury are not well understood; currently, few methods can predict the state of the cardiac muscle cell and its metabolic conditions during ischemia. Here, we explored the energetic sustainability of cardiomyocytes, using a model for cellular metabolism to predict the levels of ATP following hypoxia. We modeled glycolytic metabolism with a system of coupled ordinary differential equations describing the individual metabolic reactions within the cardiomyocyte over time. Reduced oxygen levels and ATP consumption rates were simulated to characterize metabolite responses to ischemia. By tracking biochemical species within the cell, our model enables prediction of the cell’s condition up to the moment of reperfusion. The simulations revealed a distinct transition between energetically sustainable and unsustainable ATP concentrations for various energetic demands. Our model illustrates how even low oxygen concentrations allow the cell to perform essential functions. We found that the oxygen level required for a sustainable level of ATP increases roughly linearly with the ATP consumption rate. An extracellular O2 concentration of ~0.007 mM could supply basic energy needs in non-beating cardiomyocytes, suggesting that increased collateral circulation may provide an important source of oxygen to sustain the cardiomyocyte during extended ischemia. Our model provides a time-dependent framework for studying various intervention strategies to change the outcome of reperfusion.
Project description:The purpose of this study was to investigate the hypothesis that cardiomyocyte-specific loss of the electrogenic NBCe1 Na+-HCO3- cotransporter is cardioprotective during in vivo ischemia-reperfusion (IR) injury. An NBCe1 (Slc4a4 gene) cardiac conditional knockout mouse (KO) model was prepared by gene targeting. Cardiovascular performance of wild-type (WT) and cardiac-specific NBCe1 KO mice was analyzed by intraventricular pressure measurements, and changes in cardiac gene expression were determined by RNA Seq analysis. Response to in vivo I/R injury was analyzed after 30 minutes occlusion of the left anterior descending artery followed by 3 hours of reperfusion. Loss of NBCe1 in cardiac myocytes did not impair cardiac contractility or relaxation and caused only limited changes in gene expression patterns, such as those for electrical excitability. However, following ischemia and reperfusion, KO heart sections exhibited significantly fewer apoptotic nuclei than WT sections. These studies indicate that cardiac-specific loss of NBCe1 does not impair cardiovascular performance, causes only minimal changes in gene expression patterns, and protects against I/R injury in vivo.
Project description:IgA+ Plasma Cells were sort-purified from the small intestinal lamina prorpia of mice with a B cell lineage-intrinsic deletion of Arntl (Mb1 Cre+/- x Arntl fl/fl) or Cre negative littermate controls (also deisgnated WT and KO), at two Zeitgeber time points (ZT0 and ZT12). RNA extracted from these samples was subjected to bulk RNA seq to identify time of day differences and to compare role of Arntl expression in this context.
