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(Circulation. 2005;112:I-57 – I-64.)
© 2005 American Heart Association, Inc.

Cardiac Transplantation and Surgery for Congestive Heart Failure

Gene Profiling Changes in Cytoskeletal Proteins During Clinical Recovery After Left Ventricular–Assist Device Support

Emma J. Birks, MRCP, PhD; Jennifer L. Hall, PhD; Paul J.R. Barton, PhD; Suzanne Grindle, BSc; Najma Latif, PhD; James P. Hardy, MBBS; James E. Rider, MD; Nicholas R. Banner, FRCP; Asghar Khaghani, FRCS; Leslie W. Miller, MD; Magdi H. Yacoub, FRS

From the Royal Brompton and Harefield NHS Trust (E.J.B., J.P.H., N.R.B., A.K.), Harefield, Middlesex, and the National Heart and Lung Institute (E.J.B., P.J.R.B., N.L., J.P.H., M.H.Y.), Imperial College, Heart Science Centre, London, England, and the Cardiovascular Division (J.L.H., S.G., L.W.M.), Department of Medicine, University of Minnesota, Minneapolis, Minn.

Correspondence to Sir Magdi Yacoub, FRS, Cardiothoracic Surgery, Heart Science Centre, Royal Brompton and Harefield Hospital, Harefield, Middlesex, UB9 6JH, UK. E-mail e.birks{at}ic.ac.uk

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 ß1, ß6, and 7 decreased 1.7-fold (P<0.05), 2.4-fold (P<0.05), and 1.5-fold (P<0.05), respectively, but integrins 5 and ß5 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: ß-actin increased 1.4-fold (P<0.05); -tropomyosin, 1.3-fold (P<0.05); 1-actinin, 1.8-fold (P<0.01); and -filamin A, 1.6-fold (P<0.05). Both troponin T3 and 2-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.

Key Words: heart failure • heart-assist device • myocardial contraction • remodeling • genes