Biomarkers are gaining increasing interest to predict risk but also to aid in diagnostics. Tissue-specific biomarkers are of utmost importance to detect diseases of respective organs. As of yet there are no atriumspecific biomarkers for risk stratification of atrial disease, such as atrial fibrillation. Bioinformatics such as mRNA microarrays can help to detect tissue-enriched and possibly tissue-specific expressed genes that can be targets for biomarkers. We describe an approach to identify genes preferably expressed in atrial cardiomyocytes compared with ventricular cardiomyocytes by RNA microarray and confirmed by quantitative real-time polymerase chain reaction. By this approach we identified several atrium-enriched genes but also ventricle-enriched genes. As expected atrial natriuretic peptide (ANP) mRNA showed higher expression in atrial cardiomyocytes while with adrenergic stimulation expression was almost as high in ventricular as in atrial cells. Brain-type natriuretic peptide (BNP), however, was not different between atrial and ventricular cells giving a possible explanation for increased levels of NT-proBNP in atrial fibrillation patients. Interesting identified candidates are serpine1 and ltbp2 as atrium-enriched genes whereas alpha-adrenergic receptor subtype 1b and S100A1 expression was significantly higher in ventricular cells. The identified genes need to be confirmed in human tissue and might ultimately be tested as potential biomarkers for atrial stress. (Neth Heart J 2010;18:610–4.)
This is a preview of subscription content, log in via an institution to check access.
References
Braunwald E. Biomarkers in heart failure. N Engl J Med. 2008;358:2148–2159.
Camm AJ, Kirchhof P, Lip GYH, Schotten U, Savelieva I, Ernst S, et al. Guidelines for the management of atrial fibrillation. Eur Heart J. 2010; 31:2369–2429.
Buck S, Rienstra M, Maass AH, Nieuwland W, Van Veldhuisen DJ, Van Gelder IC. Cardiac resynchronization therapy in patients with heart failure and atrial fibrillation: importance of new-onset atrial fibrillation and total atrial conduction time. Europace. 2008;10:558–565.
Cosio FG, Aliot E, Botto GL, Heidbuchel H, Geller CJ, Kirchhof P, et al. Delayed rhythm control of atrial fibrillation may be a cause of failure to prevent recurrences: reasons for change to active antiarrhythmic treatment at the time of the first detected episode. Europace. 2008;10:21–27.
Van Gelder IC, Crijns HJ, Tieleman RG, Brugemann J, De Kam PJ, Gosselink AT, et al. Chronic atrial fibrillation. Success of serial cardioversion therapy and safety of oral anticoagulation. Arch Intern Med. 1996;156:2585–2592.
Ahmed S, Rienstra M, Crijns HJ, Links TP, Wiesfeld AC, Hillege HL, et al. Continuous vs episodic prophylactic treatment with amiodarone for the prevention of atrial fibrillation: a randomized trial. JAMA. 2008;300:1784–1792.
Smit MD, Van Gelder IC. Will we be able to predict in which atrial fibrillation patients a rhythm control strategy will be successful? Europace. 2009;11:846–847.
Maass A, Langer SJ, Oberdorf-Maass S, Bauer S, Neyses L, Leinwand LA. Rational promoter selection for gene transfer into cardiac cells. J Mol Cell Cardiol. 2003;35:823–831.
Maass AH, Ikeda K, Oberdorf-Maass S, Maier SK, Leinwand LA. Hypertrophy, fibrosis, and sudden cardiac death in response to pathological stimuli in mice with mutations in cardiac troponin T. Circulation. 2004;110:2102–2109.
Cesari M, Pahor M, Incalzi RA. Plasminogen Activator Inhibitor-1 (PAI-1): A Key Factor Linking Fibrinolysis and Age-Related Subclinical and Clinical Conditions. Cardiovasc Ther. 2010;28:e72–e79.
Pretorius M, Donahue BS, Yu C, Greelish JP, Roden DM, Brown NJ. Plasminogen activator inhibitor-1 as a predictor of postoperative atrial fibrillation after cardiopulmonary bypass. Circulation. 2007;116(11 Suppl):I1–I7.
Jarai R, Kaun C, Weiss TW, Speidl WS, Rychli K, Maurer G, et al. Human cardiac fibroblasts express B-type natriuretic peptide: fluvastatin ameliorates its up-regulation by interleukin-1alpha, tumour necrosis factor-alpha and transforming growth factor-beta. J Cell Mol Med. 2009;13:4415–4421.
Burstein B, Libby E, Calderone A, Nattel S. Differential behaviors of atrial versus ventricular fibroblasts: a potential role for platelet-derived growth factor in atrial-ventricular remodeling differences. Circulation. 2008;117:1630–1641.
Patton KK, Ellinor PT, Heckbert SR, Christenson RH, DeFilippi C, Gottdiener JS, et al. N-terminal pro-B-type natriuretic peptide is a major predictor of the development of atrial fibrillation: the Cardiovascular Health Study. Circulation. 2009;120:1768–1774.
Rienstra M, Van Gelder IC, Van den Berg MP, Boomsma F, Van Veldhuisen DJ. Natriuretic peptides in patients with atrial fibrillation and advanced chronic heart failure: determinants and prognostic value of (NT-) ANP and (NT-pro)BNP. Europace. 2006;8:482–487.
Mayyas F, Niebauer M, Zurick A, Barnard J, Gillinov AM, Chung MK, et al. Association of left atrial endothelin-1 with atrial rhythm, size, and fibrosis in patients with structural heart disease. Circ Arrhythm Electrophysiol. 2010;3:369–379.
Tijsen AJ, Creemers EE, Moerland PD, de Windt LJ, van der Wal AC, Kok WE, et al. MiR423-5p as a circulating biomarker for heart failure. Circ Res. 2010;106:1035–1039.
Frost RJ, Engelhardt S. A secretion trap screen in yeast identifies protease inhibitor 16 as a novel antihypertrophic protein secreted from the heart. Circulation. 2007;116:1768–1775.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Maass, A., De Jong, AM., Frederiks, J. et al. Cardiac gene expression profiling – the quest for an atrium-specific biomarker. Neth Heart J 18, 610–614 (2010). https://doi.org/10.1007/s12471-010-0844-8
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12471-010-0844-8