Systematic name M12300
Brief description Up-regulated genesin the left ventricle myocardium of patients with heart failure following implantation of LVAD (left ventricular assist device).
Full description or abstract Chronic unloading of the failing heart with a left ventricular assist device (LVAD) can decrease cardiac mass and myocyte size and has the potential to improve contractile function. To study the effect of chronic ventricular unloading on myocardial gene expression, a microarray (U133A, Affymetrix) profiling gene expression was compared before and after LVAD support in seven patients with idiopathic dilated cardiomyopathy and end-stage heart failure. On average, 1,374 +/- 155 genes were reported as increased and 1,629 +/- 45 as decreased after LVAD support. A total of 130 gene transcripts achieved the strict criteria for upregulation and 49 gene transcripts for downregulation after LVAD support. Upregulated genes included a large proportion of transcription factors, genes related to cell growth/apoptosis/DNA repair, cell structure proteins, metabolism, and cell signaling/communication. LVAD support resulted in downregulation of genes for a group of cytokines. To validate the array data, 10 altered genes were confirmed by real-time RT-PCR. Further study showed that the phosphoinositide-3-kinase-forkhead protein pathway and proteins related to nitric oxide synthesis, including eNOS and dimethylarginine dimethylaminohydrolase isoform 1 (DDAH1, an enzyme regulating endogenous nitric oxide synthase activity), were significantly increased during the cardiac remodeling process. Increased eNOS and DDAH1 expression after LVAD support may contribute to improved endothelial function of the failing hearts.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 12824457   Authors: Chen Y,Park S,Li Y,Missov E,Hou M,Han X,Hall JL,Miller LW,Bache RJ
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Source species Homo sapiens
Contributed by John Newman (University of Washington)
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Version history 3.0: Renamed from LVAD_HEARTFAILURE_UP

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