Myocardial insulin-like growth factor-I gene expression during recovery from heart failure after combined left ventricular assist device and clenbuterol therapy

Paul J.R. Barton, Leanne E. Felkin, Emma J. Birks, Martin E. Cullen, Nicholas R. Banner, Suzanne Grindle, Jennifer L Hall, Leslie W. Miller, Magdi H. Yacoub

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

Background - Patients who undergo mechanical support with a left ventricular assist device (LVAD) exhibit reverse remodeling and in some cases recover from heart failure. We have developed a combination therapy using LVAD support combined with pharmacological therapy to maximize reverse remodeling, followed by the β2 adrenergic agonist clenbuterol. We recently found that clenbuterol induces insulin-like growth factor I (IGF-I) in cardiac myocytes in vitro. The purpose of this study is to examine IGF-I expression in recovery patients after combination therapy. Methods and Results - Myocardial mRNA levels were determined by real-time quantitative polymerase chain reaction in 12 recovery patients (at LVAD implantation, explantation, and 1 year after explantation). IGF-I mRNA was elevated at the time of LVAD explantation relative to donors, with 2 groups distinguishable: Those with low IGF-I mRNA at implantation who showed significant increase during recovery and those with high IGF-I mRNA at implantation who remained high. Levels returned to normal by 1 year after explantation. Microarray analysis of implantation and explantation samples of recovery patients further revealed elevated IGF-II and IGF binding proteins IGFBP4 and IGFBP6. IGF-I levels correlated with stromal cell-derived factor mRNA measured both in LVAD patients and in a wider cohort of heart failure patients. Conclusions - The data suggest involvement of elevated myocardial IGF-I mRNA in recovery. IGF-I may act to limit atrophy and apoptosis during reverse remodeling and to promote repair and regeneration in concert with stromal cell derived factor.

Original languageEnglish (US)
Pages (from-to)I46-I50
JournalCirculation
Volume112
Issue number9 SUPPL.
DOIs
StatePublished - Aug 30 2005

Keywords

  • Growth substances
  • Heart failure
  • Myocardium
  • Polymerase chain reaction
  • Ventricles

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