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Vol 47(2013) N 3 p. 382-388;
O.G. Polovkova1*, O.A. Makeeva1, A.A. Lezhnev2, E.V. Kulish1, V.M. Shipulin2, V.P. Puzyrev1

Expression Profiles of Calcineurin Pathway Genes in Myocardium in Relation to Ischemic Heart Remodeling in Humans

1Research Institute of Medical Genetics, Siberian Branch, Russian Academy of Medical Sciences, Tomsk, 634050 Russia
2Research Institute of Cardiology, Siberian Branch, Russian Academy of Medical Sciences, Tomsk, 634012 Russia

*oksana.ivanova@medgenetics.ru
Received - 2012-10-05; Accepted - 2012-11-29

The calcineurin signaling pathway plays a crucial role in the heart remodeling of a different nature, in the development of left ventricular dilatation, and in the progression of heart failure. Components of the calcineurin pathway are involved in the regulation of cardiomyocyte hypertrophy, angiogenesis, and apoptosis. In this study, quantitative expression profiles were determined for major calcineurin pathway genes PPP3CA, PPP3R1, PPP3CB, GATA4, and NFATC4 in the myocardium of the right atrium auricle in patients with ischemic heart disease who underwent different types of surgery depending on the severity of clinical symptoms as follows: surgical reconstruction of left ventricle (LV) geometry (post-infarction aneurysm) or coronary artery bypass grafting (unaltered LV morphology). In patients with sizable post-infarction LV dilatation (n = 21), the expression levels of calcineurin catalytic subunit genes PPP3CA and PPP3CB were 1.3 and 1.6 times lower (p = 0.018 and 0.023, respectively) than in patients with unaltered heart shape (n = 34). The differences in expression levels of PPP3R1, which encodes calcineurin regulatory subunit B and levels of GATA4 and NFATC4, which encode transcription factors, were not significant. Thus, decreased PPP3CA and PPP3CB expression in the atrial myocardium may be a marker of significant post-infarction LV remodeling. The further investigation of the relationship between expression levels of calcineurin pathway genes and the degree of myocardial damage may provide useful insights for predicting adverse events in cardiosurgical treatment of patients with postinfarction heart remodeling.

coronary heart disease, gene expression, calcineurin pathway genes, myocardium remodeling, left ventricular dilatation



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