Project description:Cardiomyopathies-associated metabolic pathologies (e.g. T2D and insulin resistance) are a leading cause of mortality. It is known that the association between the pathologies works in both directions, where heart failure can lead to metabolic derangements such as insulin resistance. This intricate crosstalk exemplifies the importance of a fine coordination between one of the most energy demanding organs and an equilibrated carbohydrate metabolism. In this light, to assist in the understanding of the role of insulin regulated glucose transporters and the development of cardiomyopathies, we set out to study GLUT12. GLUT12 is a novel insulin regulated GLUT expressed in the main insulin sensitive tissues such as cardiac and skeletal muscle and adipose tissue. This study investigates the role of GLUT12 in heart failure and diabetes by developing a model for glut12 deficiency in zebrafish.
Project description:Cardiomyopathies-associated metabolic pathologies (e.g. T2D and insulin resistance) are a leading cause of mortality. It is known that the association between the pathologies works in both directions, where heart failure can lead to metabolic derangements such as insulin resistance. This intricate crosstalk exemplifies the importance of a fine coordination between one of the most energy demanding organs and an equilibrated carbohydrate metabolism. In this light, to assist in the understanding of the role of insulin regulated glucose transporters and the development of cardiomyopathies, we set out to study GLUT12. GLUT12 is a novel insulin regulated GLUT expressed in the main insulin sensitive tissues such as cardiac and skeletal muscle and adipose tissue. This study investigates the role of GLUT12 in heart failure and diabetes by developing a model for glut12 deficiency in zebrafish. 6 samples in total were analyzed. 3 replicates from control samples (injected with contol MO) and 3 replicates from glut12 morphant samples (injected with glut12 splice MO). In each sample 10 embryos were pooled.
Project description:Reducing microtubule detyrosination has been shown to inprove contractility in heart failure cardiomyocytes. To evaluate the feasibility of targeting the detyrosinated microtubule network for treatment of cardiomyopathy in an in-vivo context we overexpressed tubulin tyrosine ligase (TTL) by AAV9 delivery in a mouse model of HCM (Mybpc3-/-) and an empty vector as control in HCM and WT mice.
Project description:The abstract of the manuscript titled "Identification of co-regulated genes and cis-regulatory modules in Drosophila contractile cardiomyocytes" is given below: "Understanding how sets of genes are co-regulated to generate cell diversity during metazoan development is a major challenge. This requires the identification of tightly co-expressed genes in a given developmental process, of the responsible cis-regulatory modules, and of the combination of trans-acting transcription factors. We chose the Drosophila cardiac tube to address this issue. The cardiac tube is composed of a rostral aorta and a caudal heart, with distinct morphologies and functions and its development is controlled by conserved transcription factors. Our goal was to identify heart specific expressed genes and to use a combination of genetic and bioinformatic tools to identify and characterize their heart cis-regulatory modules (CRMs). By combined candidate gene approach and microarray experiments, we found 15 different genes that are specifically co-expressed in the contractile cardiomyocytes of the heart. Potential heart-specific CRMs were retrieved from evolutionary conserved non-coding sequences that were ranked according to an integrated score based on combinations of conserved occurrences of potential binding sites for transcription factors known to be expressed in the cardiovascular system, namely Abd-A, Tin, GATA, Mef2, Hand, and T-box factors. Candidate CRMs were then tested in vivo by generating nGFP reporter construct transgenic flies, allowing the identification of three heart enhancers precisely reproducing endogenous gene expression in the heart. We identified 15 genes that are tightly co-regulated in the contractile cardiomyocytes of the heart and for three of them found the responsible enhancer through computational predictions. A computational post-analysis suggests that different combinations of heart transcription factors may regulate these enhancers and permits to further refine the in silico identification of heart-specific CRMs."
Project description:We report the identification of genome-wide binding site of the cardiac transcription factor Nkx2-5 during mouse heart development.
Project description:Cardiac profiling of miR expression levels in a transgenic mouse model of heart failure (MHC-CnA) to identify miRs that are co-regulated with the development of calcineurin-induced heart failure.
Project description:We report the identification of genome-wide binding site of the cardiac transcription factor Nkx2-5 during mouse heart development. Examination of Nkx2-5 binding in wild-type mouse in duplicate.
Project description:Atrial fibrillation (AF) remains challenging to prevent and treat. It is associated with increased rates of heart failure, stroke and neurological decline. A key feature of AF is atrial enlargement. However, not all atrial enlargement progresses to pathology and AF.
In the current study, we characterized mouse atria from a 1) pathological model (cardiac-specific transgenic (Tg) that develops dilated cardiomyopathy [DCM] and AF due to reduced protective signalling [PI3K]; DCM-dnPI3K), and a 2) physiological model (cardiac-specific Tg with an enlarged heart due to increased insulin-like growth factor 1 receptor; IGF1R). Atrial enlargement in the DCM-dnPI3K Tg, but not IGF1R Tg, was associated with atrial dysfunction, fibrosis and a heart failure gene expression pattern. Proteomics analysis identified proteins and pathways that were differentially regulated in pathological and physiological atrial enlargement, and provides a resource to study potential drug targets for AF.