{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T15:09:49Z","timestamp":1774796989952,"version":"3.50.1"},"reference-count":54,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,1,14]],"date-time":"2020-01-14T00:00:00Z","timestamp":1578960000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006109","name":"Vedeck\u00e1 Grantov\u00e1 Agent\u00fara M\u0160VVa\u0160 SR a SAV","doi-asserted-by":"publisher","award":["2\/0002\/20, 2\/0158\/19"],"award-info":[{"award-number":["2\/0002\/20, 2\/0158\/19"]}],"id":[{"id":"10.13039\/501100006109","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005357","name":"Agent\u00fara na Podporu V\u00fdskumu a V\u00fdvoja","doi-asserted-by":"publisher","award":["18-0548, 15-0376"],"award-info":[{"award-number":["18-0548, 15-0376"]}],"id":[{"id":"10.13039\/501100005357","id-type":"DOI","asserted-by":"publisher"}]},{"name":"EU ITMS","award":["26230120009"],"award-info":[{"award-number":["26230120009"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The arrhythmogenic potential of \u03b21-adrenoceptor autoantibodies (\u03b21-AA), as well as antiarrhythmic properties of omega-3 in heart diseases, have been reported while underlying mechanisms are poorly understood. We aimed to test our hypothesis that omega-3 (eicosapentaenoic acid-EPA, docosahexaenoic acid-DHA) may inhibit matrix metalloproteinase (MMP-2) activity to prevent cleavage of \u03b21-AR and formation of \u03b21-AA resulting in attenuation of pro-arrhythmic connexin-43 (Cx43) and protein kinase C (PKC) signaling in the diseased heart. We have demonstrated that the appearance and increase of \u03b21-AA in blood serum of male and female 12-month-old spontaneously hypertensive rats (SHR) was associated with an increase of inducible ventricular fibrillation (VF) comparing to normotensive controls. In contrast, supplementation of hypertensive rats with omega-3 for two months suppressed \u03b21-AA levels and reduced incidence of VF. Suppression of \u03b21-AA was accompanied by a decrease of elevated myocardial MMP-2 activity, preservation of cardiac cell membrane integrity and Cx43 topology. Moreover, omega-3 abrogated decline in expression of total Cx43 as well as its phosphorylated forms at serine 368 along with PKC-\u03b5, while decreased pro-fibrotic PKC-\u03b4 levels in hypertensive rat heart regardless the sex. The implication of MMP-2 in the action of omega-3 was also demonstrated in cultured cardiomyocytes in which desensitization of \u03b21-AR due to permanent activation of \u03b21-AR with isoproterenol was prevented by MMP-2 inhibitor or EPA. Collectively, these data support the notion that omega-3 via suppression of \u03b21-AA mechanistically controlled by MMP-2 may attenuate abnormal of Cx43 and PKC-\u03b5 signaling; thus, abolish arrhythmia substrate and protect rats with an advanced stage of hypertension from malignant arrhythmias.<\/jats:p>","DOI":"10.3390\/ijms21020526","type":"journal-article","created":{"date-parts":[[2020,1,15]],"date-time":"2020-01-15T10:30:27Z","timestamp":1579084227000},"page":"526","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Suppression of \u03b21-Adrenoceptor Autoantibodies is Involved in the Antiarrhythmic Effects of Omega-3 Fatty Acids in Male and Female Hypertensive Rats"],"prefix":"10.3390","volume":"21","author":[{"given":"Barbara","family":"Szeiffova Bacova","sequence":"first","affiliation":[{"name":"Centre of Experimental Medicine, Institute for Heart Research, SAS, 841 04 Bratislava, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6703-5863","authenticated-orcid":false,"given":"Jana","family":"Radosinska","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Comenius University, 81108 Bratislava, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerd","family":"Wallukat","sequence":"additional","affiliation":[{"name":"Max-Delbruck Centrum f\u00fcr Molekulare Medizine, 13125 Berlin, Germany"},{"name":"Berlin Cures GmbH, 10719 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miroslav","family":"Barancik","sequence":"additional","affiliation":[{"name":"Centre of Experimental Medicine, Institute for Heart Research, SAS, 841 04 Bratislava, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Wallukat","sequence":"additional","affiliation":[{"name":"Berlin Cures GmbH, 10719 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladimir","family":"Knezl","sequence":"additional","affiliation":[{"name":"Center of Experimental Medicine SAS, Institute of Experimental Pharmacology and Toxicology, 841 04 Bratislava, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0438-3956","authenticated-orcid":false,"given":"Matus","family":"Sykora","sequence":"additional","affiliation":[{"name":"Centre of Experimental Medicine, Institute for Heart Research, SAS, 841 04 Bratislava, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3834-7395","authenticated-orcid":false,"given":"Ludovit","family":"Paulis","sequence":"additional","affiliation":[{"name":"Institute of Pathophysiology, Faculty of Medicine, Comenius University, 81108 Bratislava, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Narcis","family":"Tribulova","sequence":"additional","affiliation":[{"name":"Centre of Experimental Medicine, Institute for Heart Research, SAS, 841 04 Bratislava, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kune\u0161, J., Kadlecov\u00e1, M., Vaneckov\u00e1, I., and Zicha, J. 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