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, JoAnn Lindenfeld, Eugene E. Wolfel, Mark Geraci, Michael R. Bristow, Joseph Cleveland

Research output: Contribution to journalArticle

14 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Hypoxia-Inducible Factor 1
Gene Expression
Equipment and Supplies
Heart Failure
Equipment Failure
Tropomyosin
Ventricular Function
Facilitative Glucose Transport Proteins
Myosin Heavy Chains
Recovery of Function
Sarcoplasmic Reticulum
Atrial Natriuretic Factor
Heart Transplantation
Regulator Genes
Genes
Adenosine Triphosphatases
Western Blotting
Messenger RNA
Antibodies
Therapeutics

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery
  • Transplantation

Cite this

Lowes, B. D., Zolty, R., Shakar, S. F., Brieke, A., Gray, N., Reed, M., ... 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

Assist Devices Fail to Reverse Patterns of Fetal Gene Expression Despite β-Blockers. / Lowes, Brian D.; Zolty, Ronald; Shakar, Simon F.; Brieke, Andreas; Gray, Norman; Reed, Michael; Calalb, Mihail; Minobe, Wayne; Lindenfeld, JoAnn; Wolfel, Eugene E.; Geraci, Mark; Bristow, Michael R.; Cleveland, Joseph.

In: Journal of Heart and Lung Transplantation, Vol. 26, No. 11, 11.2007, p. 1170-1176.

Research output: Contribution to journalArticle

Lowes, BD, Zolty, R, Shakar, SF, Brieke, A, Gray, N, Reed, M, Calalb, M, Minobe, W, Lindenfeld, J, Wolfel, EE, Geraci, M, Bristow, MR & Cleveland, J 2007, 'Assist Devices Fail to Reverse Patterns of Fetal Gene Expression Despite β-Blockers', Journal of Heart and Lung Transplantation, vol. 26, no. 11, pp. 1170-1176. https://doi.org/10.1016/j.healun.2007.08.003
Lowes, Brian D. ; Zolty, Ronald ; Shakar, Simon F. ; Brieke, Andreas ; Gray, Norman ; Reed, Michael ; Calalb, Mihail ; Minobe, Wayne ; Lindenfeld, JoAnn ; Wolfel, Eugene E. ; Geraci, Mark ; Bristow, Michael R. ; Cleveland, Joseph. / Assist Devices Fail to Reverse Patterns of Fetal Gene Expression Despite β-Blockers. In: Journal of Heart and Lung Transplantation. 2007 ; Vol. 26, No. 11. pp. 1170-1176.
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