Signalling function of β-catenin is important at early stages of adult heart pathological hypertrophy

Abstract

The spread of cardiovascular diseases, their significant threat to health and socio-economic burden result in considerable interest of scientists to this problem solution. Lately, not only investigations into new methods of diagnosis and treatment of cardiovascular disease, but also elucidation of the mechanisms underlying their occurrence and course become topical. The aim of our study was to investigate the signaling function of the canonical Wnt-signaling and b-catenin function in the development of pathological hypertrophy of the adult myocardium. Methods. Studies were conducted using transgenic mice BATGIRL and cultures of isolated cardiomyocytes. To induce pathological hypertrophy, lithium chloride and AnglI were used. Changes in the expression of hypertrophic genes and genes involved in the canonical Wnt-signaling were analyzed by real-time PCR and Western-blot analysis. Morphological studies and X-gal staining were performed. Results. Upon the action of hypertrophic stimuli the activation of b-catenin signaling function is shown to occur in the early stages of observation, as evidenced by X-gal staining and changes in gene-targets expression of this signaling (c-Fos, c-Myc, CyclinD1 and TCF-4). There was also observed an increase in the content of activated b-catenin and phosphorylated GSK3b proteins within a day after the action of angiotensin and lithium chloride in the culture of isolated cardiomyocytes. Conclusions. With the development of pathological hypertrophy due to chronic high blood pressure, there occurs the activation of many signal-regulatory mechanisms of cardiomyocytes and one of them is the canonical Wnt-signaling. However, the activation of the canonical Wnt-signaling and β-catenin, in particular, is the early event and obviously essential to run the genetic program of myocardium remodeling.Keywords: β-catenin, hypertrophy, Wnt-signaling, gene expression, myocardium.