Alterations of gene expression in failing myocardium following left ventricular assist device support

YingJie Chen, Soon Park, Yunfang Li, Emil Missov, Mingxiao Hou, Xinqiang Han, Jennifer L. Hall, Leslie W. Miller, Robert J. Bache

Research output: Contribution to journalArticle

89 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)251-260
Number of pages10
JournalPhysiological Genomics
Volume14
StatePublished - Oct 2003
Externally publishedYes

Fingerprint

Heart-Assist Devices
Myocardium
Gene Expression
Genes
Down-Regulation
Forkhead Transcription Factors
1-Phosphatidylinositol 4-Kinase
Dilated Cardiomyopathy
Gene Expression Profiling
Cardiac Myocytes
Nitric Oxide Synthase
Cell Communication
DNA Repair
Real-Time Polymerase Chain Reaction
Nitric Oxide
Protein Isoforms
Proteins
Transcription Factors
Up-Regulation
Heart Failure

Keywords

  • Congestive heart failure
  • Dilated cardiomyopathy
  • Gene profiling
  • Microarray

ASJC Scopus subject areas

  • Physiology
  • Genetics

Cite this

Chen, Y., Park, S., Li, Y., Missov, E., Hou, M., Han, X., ... Bache, R. J. (2003). Alterations of gene expression in failing myocardium following left ventricular assist device support. Physiological Genomics, 14, 251-260.

Alterations of gene expression in failing myocardium following left ventricular assist device support. / Chen, YingJie; Park, Soon; Li, Yunfang; Missov, Emil; Hou, Mingxiao; Han, Xinqiang; Hall, Jennifer L.; Miller, Leslie W.; Bache, Robert J.

In: Physiological Genomics, Vol. 14, 10.2003, p. 251-260.

Research output: Contribution to journalArticle

Chen, Y, Park, S, Li, Y, Missov, E, Hou, M, Han, X, Hall, JL, Miller, LW & Bache, RJ 2003, 'Alterations of gene expression in failing myocardium following left ventricular assist device support', Physiological Genomics, vol. 14, pp. 251-260.
Chen, YingJie ; Park, Soon ; Li, Yunfang ; Missov, Emil ; Hou, Mingxiao ; Han, Xinqiang ; Hall, Jennifer L. ; Miller, Leslie W. ; Bache, Robert J. / Alterations of gene expression in failing myocardium following left ventricular assist device support. In: Physiological Genomics. 2003 ; Vol. 14. pp. 251-260.
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