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Heart rhythm genomic fabric in hypoxia
Authors:Dumitru A Iacobas  Sanda Iacobas
Institution:a DP Purupura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, USA
b Departments of Pediatrics and Neuroscience, University of California at San Diego, CA, USA
Abstract:The molecular mechanisms by which chronic hypoxia, whether constant (CCH) or intermittent (CIH), alters the heart rhythm are still under debate. Expression level, control, maturational profile and intercoordination of 54 genes encoding heart rhythm determinants (HRDs) were analyzed in 36 mice subjected for 1, 2 or 4 weeks of their early life to normal atmospheric conditions or to CCH or CIH. Our analysis revealed a complex network of genes encoding various heart rate, inotropy and development controllers, receptors, ion channels and transporters, ankyrins, epigenetic modulators and intercalated disc components (adherens, cadherins, catenins, desmosomal, gap and tight junction proteins). The network is remodeled during maturation and substantially and differently altered by CIH and CCH. Gene Prominence Analysis that ranks the genes according to their expression stability and networking within functional gene webs, confirmed the HRD status of certain epigenetic modulators and components of the intercalated discs not yet associated with arrhythmia.
Keywords:Arrhythmia  Connexin43  Coxsackievirus and adenovirus receptor  Intercalated disc  Myocyte enhancer factors  Plakophilins
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