PS 13-18 BETA1-ADRENERGIC RECEPTOR AUTOANTIBODY PRODUCTION AND MALIGNANT ARRHYTHMIAS ARE SUPPRESSED BY OMEGA-3 FATTY ACIDS IN EXPERIMENTAL ESSENTIAL HYPERTENSION.

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Abstract
Autoantibody production to the adrenergic beta-1 receptors (b1-AAB) is known to contribute to development of dilated cardiomyopathy and arrhythmogenic substrate. Hypertension if not properly controlled is deleterious to health due to inflammation, myocardial remodelling and enhancement of b1-AAB. Cardioprotective effects of omega-3 FA supplementation are well known. We aimed to explore whether omega-3 FA intake may affect production of b1-AAB, myocardial remodelling and connexin-43 (Cx43) that ensure electric cell-to-cell coupling using aged spontaneously hypertensive rats (SHR). Male and female 12-month-old SHR as well as their age-and-sex-matched healthy Wistar rats were used. Rats fed by standard laboratory chow were compared with those supplemented with pure omega-3 ethyl ester (200 mg/kg b.w. /day) for two months. Blood serum was used for the detection of b1-AAB. Expression of Cx43, activity of matrix metalloproteinase 2 (MMP2) and ultrastructure were examined in left ventricular tissue. Susceptibility to electrically-induced ventricular fibrillation (VF) was tested using Langendorff-perfused heart. Comparing to healthy rats, male and female SHR exhibited significant increase of serum levels of b1-AAB, activity of MMP2, down-regulation and miss-localization of Cx43 and subcellular injury of the cardiomyocytes and their junctions. It was associated with higher incidence of VF. Omega-3 intake resulted in significant decrease of elevated blood pressure, b1-AAB levels and MMP2 activity in both male and female SHR. In addition, there was a clear-cut increase of Cx43 mRNA and protein expression, attenuation of Cx43 miss-localization as well as preservation of subcellular integrity of cardiomyocytes and their junctions. Incidence of VF was significantly reduced. Suppression of beta1-adrenoceptors autoantibody production is a novel mechanism implicated in cardioprotective effects of omega-3 fatty acids. It was linked with decrease of MMP-2 activity, up-regulation of myocardial Cx43, improvement of cardiomyocytes integrity and protection from VF. This work was supported by VEGA 1/0032/14, 2/0167/15, 2/0076/16 and APVV2/0348/12 grants.