Book of Abstracts - New Frontiers 2022

Abstracts of poster presentations

DISTINCT MYOCARDIAL CONNEXIN-43 ALTERATION DUE TO CARDIAC HYPERTROPHY AND ATROPHY IMPACT THE VULNERABILITY OF THE HEART TO MALIGNANT ARRHYTHMIAS

K. Andelova, M. Sykora, B. Szeiffova-Bacova, T. Egan Benova, V. Knezl, J. Slezak, N. Tribulova

Centre of Experimental Medicine, Slovak Academy of Sciences, Bratislava, Slovakia

Heart diseases related myocardial structural remodelling deteriorate heart function as well as increases susceptibility of the heart to malignant arrhythmias. One of the key factor involved in development of malignant arrhythmias are abnormalities of connexin-43 (Cx43) channels that ensure electrical coupling among cardiomyocytes to allow action potential propagation and synchronised contraction. We aimed to explore whether myocardial Cx43 protein expression and its topology differ in hypertrophied and atrophied heart as well as the impact of Cx43 changes on the susceptibility of the heart to develop ventricular fibrillation (VF). Experiments were performed using male, 2-4-month-old rats. Hypertrophied left ventricles of the of spontaneously hypertensive rats (SHR) and hyperthyroid rats (TH) as well as in atrophied left ventricle of diabetic rats (DM) and hypothyroid (HY) rats were analysed. Cx43 topology was examined using immunofluorescence labelling, while western blotting was used to determine Cx43 protein levels and its phosphorylated status related to PKC- ɛ . Isolated perfused heart was used to test its vulnerability to electrically inducible VF. Comparing to healthy controls, the left ventricular hypertrophy was associated with increased while the ventricular atrophy with decreased susceptibility of the heart to electrically inducible VF. Total Cx43 levels and its functional phosphorylated forms along with PKC- ɛ were decreased in hypertrophied myocardium while increased in atrophied ones. Moreover, there was pronounced pro-arrhythmic localisation of Cx43 on lateral sides of hypertrophied cardiomyocytes of SHR and TH rat hearts, while not in atrophied cardiomyocytes of HY and DM rat heart. Findings suggest that down-regulation of Cx43 and its altered topology in hypertrophied myocardium increase susceptibility of the heart to malignant arrhythmias. In contrast, up-regulation of Cx43 and its normal topology in atrophied myocardium may hamper development of life-threatening arrhythmias.

Funding: This study was supported by VEGA 2/0002/20, 2/0158/19 and EU-ITMS 26230120009 grants.

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