Abstract
The pathology of cardiomyocyte death during and after myocardial infarction involves both necrosis and apoptosis. Although both mechanisms lead to cell death, participation of apoptosis in this process carries the potential of developing therapies influencing at least part of the population of dying cells. Therefore the aim of this study was to determine (using oligonucleotide microarrays) expression profiles of apoptosis-regulating genes in postinfarction myocardium, comparing chronically ischemic and healthy heart muscle. Tissue samples were obtained during elective surgery from the right cardiac auricles of three patients. The expression of 141 genes involved in fibrosis was assessed using the Affymetrix HG_U133A microarray. The patients’ transcriptomes were compared using hierarchical clusterization. Differentiating genes were determined using regression analysis and Bland–Altman graph analysis. Hierarchical clusterization demonstrated that the profile of gene expression in postinfarction myocardium was different from that in the remaining specimens. Further statistical analysis showed two important differentiating genes: FOXO3A (underexpressed in post-MI sample) and CFLAR (overexpressed in post-MI sample). The expression of apoptosis-regulating genes is significantly different in post-MI myocardium from chronically ischemic and a nonischemic myocardium. Our results suggest that CFLAR is important in the induction of apoptosis in postinfarction cardiac tissue.
Similar content being viewed by others
References
Burlacu A (2003) Regulation of apoptosis by Bcl-2 family proteins. J Cell Mol Med 7:249–257
Cheng W, Kajstura J, Nitahara JA et al (1996) Programmed myocyte cell death affects the viable myocardium after infarction in rats. Exp Cell Res 226:316–327
Cross TG, Scheel-Toellner D, Henriquez NV, Deacon E, Salmon M, Lord JM (2000) Serine/threonine protein kinases and apoptosis. Exp Cell Res 256:34–41
Dąbek J, Gąsior Z, Szmagała P, Owczarek A, Kułach A, Monastyrska-Cup B, Mazurek U, Bochenek A. (2006) Expression profiles of genes associated with apoptosis assessed by oligonucleotide microarray analysis in advanced coronary artery disease and post-infarction patients. Pol Surg 8:184–187
Fan TJ, Han LH, Cong RS, Liang J (2005) Caspase family proteases and apoptosis. Acta Biochim Biophys Sin 37:719–727
Hauck L, Harms C, Grothe D, An J, Gertz K, Kronenberg G, Dietz R, Endres M, von Harsdorf R (2007) Critical role for FoxO3a-dependent regulation of p21CIP1/WAF1 in response to statin signaling in cardiac myocytes. Circ Res 100:50–60
Haupt S, Berger M, Goldberg Z, Haupt Y (2003) Apoptosis - the p53 network. J Cell Sci 116:4077–4085
Saraste A, Pulkki K (2000) Morphologic and biochemical hallmarks of apoptosis. Cardiovasc Res 45:58–37
Saraste A, Pulkki K, Kallajoki M et al (1997) Apoptosis in human acute myocardial infarction. Circulation 95:320–323
Shu HB, Halpin DR, Goeddel DV (1997) Casper is a FADD- and caspase-related inducer of apoptosis. Immunity 6:751–763
Skurk C, Izumiya Y, Maatz H, Razeghi P, Shiojima I, Sandri M, Sato K, Zeng L, Schiekofer S, Pimentel D, Lecker S, Taegtmeyer H, Goldberg AL, Walsh K (2005) The FOXO3a transcription factor regulates cardiac myocyte size downstream of AKT signaling. J Biol Chem 280:20814–20823
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Dąbek, J., Owczarek, A., Gąsior, Z. et al. Oligonucleotide Microarray Analysis of Genes Regulating Apoptosis in Chronically Ischemic and Postinfarction Myocardium. Biochem Genet 46, 241–247 (2008). https://doi.org/10.1007/s10528-007-9137-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10528-007-9137-3