18 research outputs found
Complete cardiac regeneration in a mouse model of myocardial infarction
Get PDFCardiac remodeling and subsequent heart failure remain critical issues after myocardial infarction despite improved treatment and reperfusion strategies. Recently, complete cardiac regeneration has been demonstrated in fish and newborn mice following resection of the cardiac apex. However, it remained entirely unclear whether the mammalian heart can also completely regenerate following a complex cardiac ischemic injury. We established a protocol to induce a severe heart attack in one-day-old mice using left anterior descending artery (LAD) ligation. LAD ligation triggered substantial cardiac injury in the left ventricle defined by Caspase 3 activation and massive cell death. Ischemia-induced cardiomyocyte death was also visible on day 4 after LAD ligation. Remarkably, 7 days after the initial ischemic insult, we observed complete cardiac regeneration without any signs of tissue damage or scarring. This tissue regeneration translated into long-term normal heart functions as assessed by echocardiography. In contrast, LAD ligations in 7-day-old mice resulted in extensive scarring comparable to adult mice, indicating that the regenerative capacity for complete cardiac healing after heart attacks can be traced to the first week after birth. RNAseq analyses of hearts on day 1, day 3, and day 10 and comparing LAD-ligated and sham-operated mice surprisingly revealed a transcriptional programme of major changes in genes mediating mitosis and cell division between days 1, 3 and 10 postnatally and a very limited set of genes, including genes regulating cell cycle and extracellular matrix synthesis, being differentially regulated in the regenerating hearts. We present for the first time a mammalian model of complete cardiac regeneration following a severe ischemic cardiac injury. This novel model system provides the unique opportunity to uncover molecular and cellular pathways that can induce cardiac regeneration after ischemic injury, findings that one day could be translated to human heart attack patients
Supratentorial and spinal pediatric ependymomas display a hypermethylated phenotype which includes the loss of tumor suppressor genes involved in the control of cell growth and death
No full textTargeted Sequencing of Sorted Peripheral Blood Cells Reveals Novel Germline and Somatic Variants in the Polymorphonuclear and Mononuclear Cells of Patients with Essential Thrombocythemia, Polycythemia Vera and Primary Myelofibrosis
No full textDNA Methylation Profiling of Sorted Peripheral Blood Cells Using Microarray and Next Generation Sequencing Reveals Distinct Molecular Signatures in the Polymorphonuclear and Mononuclear Cells of Patients with Essential Thrombocythemia, Polycythemia Vera and Primary Myelofibrosis
No full textGenetic Analysis of the Cardiac Methylome at Single Nucleotide Resolution in a Model of Human Cardiovascular Disease
Get PDF10.1371/journal.pgen.1004813PLoS Genetics101
Targeted sequencing of sorted peripheral blood cells reveals novel germline and somatic variants in the polymorphonuclear and mononuclear cells of patients with essential thrombocythemia, polycythemia vera and primary myelofibrosis
No full textGene Expression Profiling of Sorted Peripheral Blood Cells Using Microarray and Next Generation Sequencing Reveals Distinct Molecular Signatures in the Polymorphonuclear and Mononuclear Cells of Patients with Polycythemia Vera and Primary Myelofibrosis
No full textGene expression profiling of sorted peripheral blood cells using microarray and next generation sequencing reveals distinct molecular signatures in the polymorphonuclear and mononuclear cells of patients with polycythemia vera and primary myelofibrosis
No full textGenome-wide molecular characterization of central nervous system primitive neuroectodermal tumor and pineoblastoma
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