Proteomic profiling of the human failing heart after left ventricular assist device support.

Abstract

BACKGROUND:

Left ventricular assist device (LVAD) support is commonly used in patients with heart failure as a bridge to heart transplantation. Whereas myocardial gene expression profile changes have been well established after LVAD support, the consequences on the protein level largely remain unclear.

METHODS:

Pre-LVAD and post-LVAD myocardial tissue specimens from dilated cardiomyopathy (DCM) and ischemic heart disease (IHD) patients were analyzed by fluorescent 2-dimensional difference gel electrophoresis, and differentially expressed proteins were identified by mass spectrometry.

RESULTS:

In the DCM group, 16 proteins were detected that showed statistically significant downregulation from pre-LVAD to post-LVAD tissue. In IHD patients, 50 alterations were found, including upregulated (n = 12) and downregulated (n = 38) proteins. The identified proteins in both groups partially overlapped and included proteins from cytoskeleton and mitochondrial energy metabolism. The latter changes were paralleled by severe abnormalities in mitochondrial morphology, as shown by electron microscopy. Post-LVAD proteomes of both DCM and IHD patients largely mimicked the protein profiles of non-failing hearts. Downregulation of the serine protease inhibitor α-1-antichymotrypsin in both DCM and IHD patients after LVAD support was confirmed by immunosorbent assay.

CONCLUSIONS:

LVAD-induced cardiac remodeling in DCM and IHD patients is associated with downregulation of α-1-antichymotrypsin and specific atrophic changes in protein expression profiles predominantly involved in cytoskeleton integrity and mitochondrial energy metabolism.

• Authors: Roel A de Weger, Marguerite E I Schipper, Erica Siera-de Koning, Petra van der Weide, Matthijs F M van Oosterhout, Razi Quadir, Helga Steenbergen-Nakken, Jaap R Lahpor, Nicolaas de Jonge, Niels Bovenschen
• Journal: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation (J Heart Lung Transplant) Vol. 30 Issue 5 Pg. 497-506 (May 2011) ISSN: 1557-3117 [Electronic] United States
• PMID: 21211997 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Cytoskeletal Proteins
• Mitochondrial Proteins
• Proteome
• alpha 1-Antichymotrypsin

Topics

• Adult
• Cardiomyopathy, Dilated (metabolism, therapy)
• Cytoskeletal Proteins (metabolism)
• Energy Metabolism (physiology)
• Female
• Gene Expression Profiling
• Heart Failure (metabolism, therapy)
• Heart-Assist Devices
• Humans
• Male
• Middle Aged
• Mitochondrial Proteins (metabolism)
• Myocardial Ischemia (metabolism, therapy)
• Proteome (metabolism)
• Retrospective Studies
• alpha 1-Antichymotrypsin (metabolism)