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      Omega-3 Index and Anti-Arrhythmic Potential of Omega-3 PUFAs

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          Abstract

          Omega-3 polyunsaturated fatty acids (PUFAs), namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are permanent subjects of interest in relation to the protection of cardiovascular health and the prevention of the incidence of both ventricular and atrial arrhythmias. The purpose of this updated review is to focus on the novel cellular and molecular effects of omega-3 PUFAs, in the context of the mechanisms and factors involved in the development of cardiac arrhythmias; to provide results of the most recent studies on the omega-3 PUFA anti-arrhythmic efficacy and to discuss the lack of the benefit in relation to omega-3 PUFA status. The evidence is in the favor of omega-3 PUFA acute and long-term treatment, perhaps with mitochondria-targeted antioxidants. However, for a more objective evaluation of the anti-arrhythmic potential of omega-3 PUFAs in clinical trials, it is necessary to monitor the basal pre-interventional omega-3 status of individuals, i.e., red blood cell content, omega-3 index and free plasma levels. In the view of evidence-based medicine, it seems to be crucial to aim to establish new approaches in the prevention of cardiac arrhythmias and associated morbidity and mortality that comes with these conditions.

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          Most cited references119

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          The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2.

          MicroRNAs (miRNAs) are endogenous noncoding RNAs, about 22 nucleotides in length, that mediate post-transcriptional gene silencing by annealing to inexactly complementary sequences in the 3'-untranslated regions of target mRNAs. Our current understanding of the functions of miRNAs relies mainly on their tissue-specific or developmental stage-dependent expression and their evolutionary conservation, and therefore is primarily limited to their involvement in developmental regulation and oncogenesis. Of more than 300 miRNAs that have been identified, miR-1 and miR-133 are considered to be muscle specific. Here we show that miR-1 is overexpressed in individuals with coronary artery disease, and that when overexpressed in normal or infarcted rat hearts, it exacerbates arrhythmogenesis. Elimination of miR-1 by an antisense inhibitor in infarcted rat hearts relieved arrhythmogenesis. miR-1 overexpression slowed conduction and depolarized the cytoplasmic membrane by post-transcriptionally repressing KCNJ2 (which encodes the K(+) channel subunit Kir2.1) and GJA1 (which encodes connexin 43), and this likely accounts at least in part for its arrhythmogenic potential. Thus, miR-1 may have important pathophysiological functions in the heart, and is a potential antiarrhythmic target.
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            Cellular and molecular electrophysiology of atrial fibrillation initiation, maintenance, and progression.

            Atrial fibrillation (AF) is the most common clinically relevant arrhythmia and is associated with increased morbidity and mortality. The incidence of AF is expected to continue to rise with the aging of the population. AF is generally considered to be a progressive condition, occurring first in a paroxysmal form, then in persistent, and then long-standing persistent (chronic or permanent) forms. However, not all patients go through every phase, and the time spent in each can vary widely. Research over the past decades has identified a multitude of pathophysiological processes contributing to the initiation, maintenance, and progression of AF. However, many aspects of AF pathophysiology remain incompletely understood. In this review, we discuss the cellular and molecular electrophysiology of AF initiation, maintenance, and progression, predominantly based on recent data obtained in human tissue and animal models. The central role of Ca(2+)-handling abnormalities in both focal ectopic activity and AF substrate progression is discussed, along with the underlying molecular basis. We also deal with the ionic determinants that govern AF initiation and maintenance, as well as the structural remodeling that stabilizes AF-maintaining re-entrant mechanisms and finally makes the arrhythmia refractory to therapy. In addition, we highlight important gaps in our current understanding, particularly with respect to the translation of these concepts to the clinical setting. Ultimately, a comprehensive understanding of AF pathophysiology is expected to foster the development of improved pharmacological and nonpharmacological therapeutic approaches and to greatly improve clinical management.
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              Modifiable Risk Factors and Atrial Fibrillation.

              There has been increasing focus on the rising burden of atrial fibrillation (AF) since the turn of the millennium. The AF epidemic is projected not only to have an impact on morbidity and mortality, but also to result in increasing healthcare use and cost. Intensive research over the previous decades has improved our understanding of this complex arrhythmia while unraveling more knowledge gaps and inadequacies of current therapeutic options. Specifically, the advances in catheter ablation technology and strategies have not translated into significant gains in procedural success rates over recent years. Therefore, strategies aiming at lowering the risk of AF development and progression are urgently needed to curtail the AF epidemic and improve outcomes in affected individuals. Recent research has highlighted the potential beneficial effects of lifestyle and risk factor management for AF as upstream noninvasive therapy. The evidence supporting this treatment paradigm beyond routine clinical AF management argues for change in the delivery of care to patients who have this debilitating arrhythmia. In this review, we highlight the contributory role of risk factors to AF pathogenesis from both bench and bedside studies. Next, we discuss the rationale and potential benefits of risk factor modification for sinus rhythm maintenance. Last, we propose an integrated care model to incorporate risk factor modification as the fourth pillar of AF care in conjunction with established pillars of rate control, rhythm control, and anticoagulation therapy.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                30 October 2017
                November 2017
                : 9
                : 11
                : 1191
                Affiliations
                [1 ]Institute for Heart Research, Slovak Academy of Sciences, Dubravska cesta 9, P.O. Box 104, 84005 Bratislava, Slovakia; barbara.bacova@ 123456savba.sk (B.S.B.); tamara.benova@ 123456savba.sk (T.E.B.); miroslav.barancik@ 123456savba.sk (M.B.); jan.slezak@ 123456savba.sk (J.S.)
                [2 ]Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Dubravska cesta 9, 84104 Bratislava, Slovakia; vladimir.knezl@ 123456savba.sk
                Author notes
                [* ]Correspondence: narcisa.tribulova@ 123456savba.sk ; Tel.: +421-2-3229-5403
                Article
                nutrients-09-01191
                10.3390/nu9111191
                5707663
                29084142
                d04a3930-26ee-42c6-bb08-cc5531212da9
                © 2017 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 02 September 2017
                : 23 October 2017
                Categories
                Review

                Nutrition & Dietetics
                omega-3 pufas,omega-3 index,connexin-43,atrial fibrillation,ventricular fibrillation

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