Neil J Nosworthy, University of Sydney, New South Wales, Australia
Masako Tsubakihara, University of Sydney, New South Wales, Australia
Cristobal G dos Remedios, University of Sydney, New South Wales, Australia
Published online: September 2006
DOI: 10.1002/9780470015902.a0006225
Recent developments in microarray technology in determining the protein and gene content of cellular extracts will allow, on a much larger scale, the characterization of genes and proteins that change due to heart failure.
Keywords: microarrays; cardiomyopathy; heart failure; apoptosis; genomics
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Figure 1. Scanned images of 96 gene arrays from Clive and Vera Ramaciotti consortium, University of NSW, Australia. The genes are spotted in duplicate. Green spots (e.g. actin) indicate genes that are upregulated, orange spots (e.g. tubulin) indicate genes that are downregulated while yellow spots (e.g. myosin) show genes that have equal expression in donor and diseased hearts. Bright spots indicate a large amount of gene present, while no color means the gene is absent in the sample.
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Figure 2. Pie chart illustrating a quarter (24×25 spots) of a Micromax gene array in which mRNAs from human left ventricles are compared. The diameter of the pie represents the expression level of each spotted gene (the stronger the gene expression, the larger the diameter) and dark and light shadings indicate the expression in DCM and donor heart respectively. Equal gene expression divides a pie in half.
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Figure 3. Apoptosis signaling pathways. Upon induction of apoptosis through the Fas signaling pathway, there is an alteration in the permeability of mitochondrial membranes. This change causes the release of cytochrome c from mitochondria (Mito) into the cytoplasm, which in turn activates cascades of caspases. The Bcl-2 family of proteins regulates cell death by controlling mitochondrial membrane permeability.
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| References | |
| Barrans JD, Stamatiou D and Liew CC (2001) Construction of a human cardiovascular cDNA microarray: portrait of the failing heart. Biochemical and Biophysical Research Communications 280: 964–969. | |
| Corbett JM, Why HJ, Wheeler CH, et al. (1998) Cardiac protein abnormalities in dilated cardiomyopathy detected by two-dimensional polyacrylamide gel electrophoresis. Electrophoresis 19: 2031–2042. | |
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| Jiang LL, Tsubakihara M, Heinke MY, et al. (2001) Heart failure and apoptosis: electrophoretic methods support data from micro- and macro-arrays. A critical review of genomics and proteomics. Proteomics 1: 1481–1488. | |
| Narula J, Haider N, Virmani R, et al. (1996) Apoptosis in myocytes in end-stage heart failure. New England Journal of Medicine 335: 1182–1189. | |
| Stanton LW, Garrard LJ, Damm D, et al. (2000) Altered patterns of gene expression in response to myocardial infarction. Circulation Research 86: 939–945. | |
| Xu B, Sakkas LI, Slachta CA, et al. (2001) Apoptosis in chronic rejection of human cardiac allografts. Transplantation 71: 1137–1146. | |
| Yang JC, Moravec CS, Sussman MA, et al. (2000) Decreased SLIM1 expression and increased gelsolin expression in failing human hearts measured by high-density oligonucleotide arrays. Circulation 102: 3046–3052. | |
| Further Reading | |
| Budihardjo I, Oliver H, Lutter M, Luo X and Wang X (1999) Biochemical pathways of caspase activation during apoptosis. Annual Review of Cell and Developmental Biology 15: 269–290. | |
| Chien KR (2000) Genomic circuits and the integrative biology of cardiac diseases. Nature 407: 227–232. | |
| Hengartner MO (2000) The biochemistry of apoptosis. Nature 407: 770–776. | |
| Jenkins RE and Pennington SR (2001) Arrays for protein expression profiling: towards a viable alternative to two-dimensional gel electrophoresis? Proteomics 1: 13–29. | |
| Mogensen J, Klausen IC, Pedersen AK, et al. (1999) Alpha-cardiac actin is a novel disease gene in familial hypertrophic cardiomyopathy. Journal of Clinical Investigation 103: R39–R43. | |
| Neuss M, Crow MT, Chesley A and Lakatta EG (2001) Apoptosis in cardiac disease – What is it? – How does it occur? Cardiovascular Drugs and Therapy 15: 507–523. | |
| Seidman JG and Seidman C (2001) The genetic basis for cardiomyopathy: from mutation identification to mechanistic paradigms. Cell 104: 557–567. | |
| Towbin JA and Bowles NE (2002) The failing heart. Nature 415: 227–233. | |
| Wettschureck N, Rutten H, Zywietz A, et al. (2001) Absence of pressure overload induced myocardial hypertrophy after conditional inactivation of Galphaq/Galpha11 in cardiomyocytes. Nature Medicine 7: 1236–1240. | |
| Zhu H, Bilgin M, Bangham R, et al. (2001) Global analysis of protein activities using proteome chips. Science 293: 2101–2105. | |
| Web Links | |
| ePath Database for proteins identified on 2-D PAGE maps of ventricle and atrium of human myocardium http://www.harefield.nthames.nhs.uk/nhli/protein/index.html | |
| ePath Clive and Vera Ramaciotti consortium, University of New South Wales, Australia http://www.genomics.unsw.edu.au/CVRCGFA_labs.html | |
| ePath Micromax array from Perkin Elmer http://lifesciences.perkinelmer.com/ | |
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