Assist Devices Fail to Reverse Patterns of Fetal Gene Expression Despite β-Blockers

Brian D. Lowes, Ronald Zolty, Simon F. Shakar, Andreas Brieke, Norman Gray, Michael Reed, Mihail Calalb, Wayne Minobe, Jo Ann Lindenfeld, Eugene E. Wolfel, Mark Geraci, Michael R. Bristow, Joseph Cleveland

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Background: Heart failure is associated with reversal to a fetal gene expression pattern of contractile and metabolic genes. Substantial recovery of ventricular function with assist devices is rare. Our goal was to evaluate the effects of assist devices on fetal gene expression and hypoxia inducible factor-1α (HIF-1α), a transcriptional factor in hypoxic signaling. Methods: Human heart tissue was obtained from the left ventricular apex at the time of assist device implantation and again from the left ventricular free wall during cardiac transplantation. Non-failing tissue was obtained from unused hearts from human donors. Gene expression was measured with the Affymetrix 133 plus 2 Array. HIF-1α was measured by Western blotting with commercially available antibodies. Results: Heart failure was associated with a decrease in α-myosin heavy chain and sarcoplasmic reticulum-Ca2+ adenosine triphosphatase messenger RNA expression along with an increase in skeletal tropomyosin. This pattern persisted after assist device therapy. Heart failure was also associated with abnormalities in regulatory metabolic genes including glucose transporter 1 (GLUT1). These patterns also persisted after assist device therapy despite a reduction in atrial natriuretic peptide expression and normalization of HIF-1α. Conclusions: Failure of assist devices to produce sustained recovery of myocardial contractile function may be due in part to persistent fetal transcriptional patterns of contractile and metabolic genes.

Original languageEnglish (US)
Pages (from-to)1170-1176
Number of pages7
JournalJournal of Heart and Lung Transplantation
Volume26
Issue number11
DOIs
StatePublished - Nov 2007

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

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    Lowes, B. D., Zolty, R., Shakar, S. F., Brieke, A., Gray, N., Reed, M., Calalb, M., Minobe, W., Lindenfeld, J. A., Wolfel, E. E., Geraci, M., Bristow, M. R., & Cleveland, J. (2007). Assist Devices Fail to Reverse Patterns of Fetal Gene Expression Despite β-Blockers. Journal of Heart and Lung Transplantation, 26(11), 1170-1176. https://doi.org/10.1016/j.healun.2007.08.003