Gene profiling changes in cytoskeletal proteins during clinical recovery after left ventricular-assist device support.

Abstract

BACKGROUND:

After left ventricular-assist device (LVAD) support, a proportion of patients recover sufficient ventricular function to enable explantation of the device. The exact molecular mechanisms involved in myocardial recovery remain unknown. Cytoskeletal proteins are essential for the structure and function of the cardiac myocyte and might play a major role.

METHODS AND RESULTS:

A total of 15 patients with nonischemic cardiomyopathy who required LVAD implantation were studied; 6 recovered sufficiently to allow explantation of the device compared with 9 who did not recover and required transplantation. LV myocardial samples were collected at implantation and explantation/transplantation. Affymetrix microarray analysis was performed on the paired samples and analyzed with reference to sarcomeric and nonsarcomeric cytoskeletal proteins. In the recovery group, of the nonsarcomeric proteins, lamin A/C increased 1.5-fold (P<0.05) and spectrin 1.6-fold (P<0.05) between the times of implantation and explantation. Integrins beta1, beta6, and alpha7 decreased 1.7-fold (P<0.05), 2.4-fold (P<0.05), and 1.5-fold (P<0.05), respectively, but integrins alpha5 and beta5 increased 2.3-fold (P<0.01) and 1.2-fold (P<0.01) at explantation. The following sarcomeric proteins changed in the recovered group only: beta-actin increased 1.4-fold (P<0.05); alpha-tropomyosin, 1.3-fold (P<0.05); alpha1-actinin, 1.8-fold (P<0.01); and alpha-filamin A, 1.6-fold (P<0.05). Both troponin T3 and alpha2-actinin decreased by 1.6-fold at the time of explantation (P<0.05). Vinculin decreased 1.7-fold (P=0.001) in the recovered group but increased by 1.7-fold (P<0.05) in the nonrecovered group. Vinculin protein levels decreased 4.1-fold in the recovered group.

CONCLUSIONS:

Myocardial recovery was associated with a specific pattern of changes in sarcomeric, nonsarcomeric, and membrane-associated proteins, which could have important implications in understanding the mechanisms involved.

• Authors: Emma J Birks, Jennifer L Hall, Paul J R Barton, Suzanne Grindle, Najma Latif, James P Hardy, James E Rider, Nicholas R Banner, Asghar Khaghani, Leslie W Miller, Magdi H Yacoub
• Journal: Circulation (Circulation) Vol. 112 Issue 9 Suppl Pg. I57-64 (Aug 30 2005) ISSN: 1524-4539 [Electronic] United States
• PMID: 16159866 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic beta-2 Receptor Agonists
• Adrenergic beta-Agonists
• Cardiovascular Agents
• Cytoskeletal Proteins
• Integrins
• Clenbuterol

Topics

• Adrenergic beta-2 Receptor Agonists
• Adrenergic beta-Agonists (therapeutic use)
• Adult
• Cardiomyopathies (complications, drug therapy, genetics, metabolism, surgery)
• Cardiovascular Agents (therapeutic use)
• Clenbuterol (therapeutic use)
• Combined Modality Therapy
• Convalescence
• Cytoskeletal Proteins (biosynthesis, genetics)
• Device Removal
• Female
• Gene Expression Profiling
• Heart Failure (drug therapy, etiology, genetics, surgery)
• Heart-Assist Devices
• Hemodynamics
• Humans
• Integrins (biosynthesis, genetics)
• Male
• Middle Aged
• Myocytes, Cardiac (metabolism)
• Oligonucleotide Array Sequence Analysis
• Postoperative Period
• Reverse Transcriptase Polymerase Chain Reaction
• Treatment Outcome