Assist Devices Fail to Reverse Patterns of Fetal Gene Expression Despite β-Blockers
| Autor: | JoAnn Lindenfeld, Eugene E. Wolfel, Norman Gray, Simon F. Shakar, Wayne Minobe, Mihail Calalb, Ronald Zolty, Mark W. Geraci, Brian D. Lowes, Joseph C. Cleveland, Michael Reed, Andreas Brieke, Michael R. Bristow |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Pulmonary and Respiratory Medicine medicine.medical_specialty Adrenergic beta-Antagonists Angiotensin-Converting Enzyme Inhibitors Tropomyosin Protein Serine-Threonine Kinases Article Sarcoplasmic Reticulum Calcium-Transporting ATPases Atrial natriuretic peptide Internal medicine Gene expression medicine Humans Mineralocorticoid Receptor Antagonists Oligonucleotide Array Sequence Analysis Heart Failure Regulation of gene expression Glucose Transporter Type 1 Transplantation Myosin Heavy Chains biology business.industry Gene Expression Profiling Gene Expression Regulation Developmental Pyruvate Dehydrogenase Acetyl-Transferring Kinase Middle Aged Hypoxia (medical) Hypoxia-Inducible Factor 1 alpha Subunit medicine.disease Myocardial Contraction Gene expression profiling Endocrinology Gene Expression Regulation Heart failure biology.protein Surgery GLUT1 Heart-Assist Devices medicine.symptom Cardiology and Cardiovascular Medicine business Atrial Natriuretic Factor |
| Zdroj: | The Journal of Heart and Lung Transplantation. 26:1170-1176 |
| ISSN: | 1053-2498 |
| Popis: | 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-Ca 2+ 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. |
| Databáze: | OpenAIRE |
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