Omega-3 fatty acids and atorvastatin suppress ventricular fibrillation inducibility in hypertriglyceridemic rat hearts: implication of intracellular coupling protein, connexin-43

B Bacova, J Radosinska, V Knezl, L Kolenova, P Weismann, J Navarova, M Barancik, M Mitasikova, N Tribulova
2010 Journal of Physiology and Pharmacology  
Omega-3 fatty acids (omega-3 FA) and statins exhibit besides lipid-lowering effects the antiarrhythmic ability in clinic, while definite mechanisms are not yet elucidated. Our goal was to examine whether these compounds can modulate inducibility of hypertriglyceridemic (HTG) rat heart to ventricular fibrillation (VF) and myocardial cell-to-cell coupling protein connexin-43 (Cx43). HTG and healthy Wistar rats were orally treated with omega-3 FA(30 mg/100 g/day/2 mth) and atorvastatin (Ato, 0.5
more » ... astatin (Ato, 0.5 mg/100 g/day/2 mth) and compared to untreated rats. Susceptibility of the heart to electrically-inducible VF and functional parameters were monitored using Langendorff-perfused isolated heart. Ventricular tissues from treated and untreated HTG and Wistar rat hearts were processed for ultrastructure examination as well as for analysis of myocardial Cx43 distribution and expression using antiCx43 MAB, immunofluorescence and immunoblotting. Both, omega-3 FA and atorvastatin reduced elevated blood pressure, triglycerides and heart rate in HTG rats. Compared to Wistar the threshold to induce VF was lower in HTG rat hearts, which exhibited abnormal Cx43 distribution, decreased immunostaining and elevated phosphorylated form of Cx43. In contrast, an enhancement of immunostaining of Cx43, suppression of hyperphosphorylation of Cx43 and improvement of cardiomyocyte and intercellular junction integrity by omega-3 FA and atorvastatin was associated with a significant increase of threshold for VF. Moreover, treatment resulted in up-regulation of myocardial Cx43 and increase of VF threshold in healthy rats that was associated with up-regulation of Cx43. Results indicate that antiarrhythmic effects of omega-3 FA and atorvastatin are linked with modulation of expression and/or phosphorylation of Cx43 and protection of cardiomyocyte and cell-to-cell junction integrity. As both compounds are ligands for PPAR, a possible regulation of Cx43 gene expression and pathways involved in Cx43 phosphorylation should be investigated.
pmid:21224503 fatcat:mjoiedpqx5fmvoozeuzoi7accm