Cardiac protein abnormalities in dilated cardiomyopathy detected by two‐dimensional polyacrylamide gel electrophoresis

Electrophoresis - Tập 19 Số 11 - Trang 2031-2042 - 1998
Joseph M. Corbett1, Howard Why2, Colin Wheeler1, P J Richardson2, L. C. Archard3, Magdi H. Yacoub1, Michael J. Dunn1
1Department of Cardiothoracic Surgery, National Heart and Lung Institute, Imperial College School of Medicine, London, UK
2Cardiac Department, King’s College Hospital, London, UK
3Department of Biochemistry, Charing Cross Campus, Imperial College School of Medicine, London, UK

Tóm tắt

Abstract

The aim of the investigation was to determine whether there are specific global quantitative and qualitative changes in protein expression in heart tissue from patients with dilated cardiomyopathy (DCM) compared with ischaemic heart disease and undiseased tissue. Two‐dimensional (2‐D) polyacrylamide gel electrophoresis and computer analysis was used to study protein alteration in DCM biopsy material (n=28) compared with donor heart biopsy samples (n=9) and explanted hearts from individuals suffering from ischaemic heart disease (IHD; n = 21). A total of 88 proteins displayed decreased abundance in DCM versus IHD material while five proteins had elevated levels in the DCM group (p<0.01). The most prominent changes occurred in the contractile protein myosin light chain 2 and in a group of proteins identified as desmin. These changes do not appear to be artefactual degradation events occurring during sample processing. These proteins are not apparent in electrophoretic separations of vascular tissue or cultured endothelial cells, mesothelial cells or cardiac fibroblasts, which are clearly distinguishable from the 2‐D protein patterns of whole heart and of isolated cardiac myocytes and do not appear to reflect variations in the cellular composition of biopsy samples. The different protein patterns observed in cardiomyopathy showed no obvious relationship with New York Heart Association (NYHA) functional class or haemodynamic parameters. The study has demonstrated significant alterations in quantitative protein expression in the DCM heart which would have serious implications for myocyte function. These changes might be explained by altered protease activity in DCM which could exacerbate contractile dysfunction in the failing heart.

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Tài liệu tham khảo

10.1161/01.CIR.93.5.841

Abelmann W. H., 1988, New Concepts in Viral Heart Disease, 2

10.1161/01.CIR.82.4.1249

10.1007/BF00265923

10.1016/0006-2952(90)90147-D

10.1172/JCI114429

10.1172/JCI115969

10.1161/01.RES.72.2.463

Schaub M. C., 1987, Basic. Res. Cardiol., 82, 357

10.1161/01.RES.53.1.52

10.1016/S0021-9258(19)41496-8

10.1042/bst0250248

10.1161/01.CIR.89.6.2582

10.1016/0003-2697(76)90527-3

10.1093/eurheartj/12.suppl_D.44

Anderson N. L., 1988, Two‐Dimensional Electrophoresis: Operation of the ISO‐DALT System

10.1016/S0021-9258(18)83728-0

Krauss M. R., 1990, BioTechniques, 8, 218

10.1002/elps.11501501209

10.1002/elps.1150180322

10.1016/0167-5273(94)02198-R

10.1007/BF01907127

Ansari A. A., 1994, J. Immunol., 153, 4754, 10.4049/jimmunol.153.10.4754

10.1016/0925-4439(93)90035-Y

Khuchua Z. A., 1992, Am. J. Cardiovasc. Pathol., 4, 223

10.1161/01.RES.78.5.893

10.1161/01.RES.57.5.729

10.1007/BF02193873

10.1161/01.RES.70.5.1035

10.1016/0167-5273(92)90302-J

10.1002/elps.1150110412

10.1006/jmcc.1993.1067

Margossian S. S., 1985, J. Biol. Chem., 260, 13747, 10.1016/S0021-9258(17)38789-6

10.1161/01.CIR.85.5.1720

10.1093/eurheartj/15.suppl_3.219

10.1161/01.CIR.83.2.504

Wilke A., 1995, Herz, 20, 95

Tibbetts R. S., 1994, J. Immunol., 152, 1493, 10.4049/jimmunol.152.3.1493

10.1016/S0065-1281(83)80011-7

Sohar I., 1982, Acta Physiol. Acad. Sci. Hung., 60, 43

10.1002/mus.880040308

10.1083/jcb.82.3.811

Fagan J. M., 1992, Am. J. Physiol., 262, E637

10.1042/bj3080057

10.1016/0167-4889(95)00024-M

10.1271/bbb.59.896

10.1002/mus.880100111

10.1253/jcj.59.40

10.1161/01.RES.77.3.603

10.1111/j.1749-6632.1979.tb56511.x

10.1002/elps.1150180333

10.1002/elps.1150170140

10.1006/jmcc.1996.0317

10.1002/elps.11501601192

10.1002/elps.11501301159

10.1002/elps.1150150197

10.1002/elps.1150171107

10.1002/elps.1150170818

10.1002/elps.1150181504

10.1002/elps.1150170324

10.1002/elps.1150170431

Knecht M., 1994, Eur. J. Clin. Chem. Clin. Biochem., 32, 615

10.1093/eurheartj/15.suppl_D.37

10.1002/elps.11501601139

10.1002/elps.1150181504

10.1002/elps.1150170330

10.1002/elps.1150171027

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Electrophoresis

Tập 19 Số 11

2031-2042

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