Effect of eicosapentaenoic acid and pitavastatin on electrophysiology and anticoagulant gene expression in mice with rapid atrial pacing

Abstract

Abstract. Atrial remodeling is considered to be any persistent change in atrial structure or function, and is responsible for the development and perpetuation of atrial fibrillation (AF). Oxidative stress and intracellular pH regulation may also be linked to AF; however it remains unclear whether eicosapentaenoic acid (EPA) or statins have beneficial therapeutic effects. The aim of the present study was to investigate the effects of EPA and pitavastatin on the electrophysiology of and gene expressions in mice with rapidly-paced atria. Mice were treated with EPA (10 mg/g/day) or pitavastatin (30 ng/g/day) for 6 weeks, following which AF was simulated by 8-h atrial pacing at 1,800 bpm. The atrial electrophysiological properties and the expression of cardiac genes, potassium voltage-gated channel subfamily A member 5 (Kcna5), Kcn subfamily D member 2 (Kcnd2), Kv channel-interacting protein 2 (KChIP2), solute carrier family 9 member A1, thrombomodulin (TM) and tissue factor pathway inhibitor (TFPI) were examined using reverse transcription-quantitative polymerase chain reaction. In control mice, significant atrial electrical remodeling was observed (P<0.05); however, treatment with either EPA or pitavastatin ameliorated these electrophysiological changes (P>0.05). mRNA levels of Kcnd2, KChIP2 and Kcna5 were significantly upregulated in control mice (P<0.05), whereas treatment with EPA or pitavastatin attenuated this upregulation (P>0.05). Administration of pitavastatin significantly reduced the downregulation of both TFPI and TM (P<0.05). EPA treatment attenuated the TFPI downregulation compared with control mice (P>0.05), however no significant effect on TM expression was observed. In addition, both EPA (P>0.05) and pitavastatin (P<0.05) suppressed the overexpression of endothelial nitric oxide synthase. This was also exhibited in Ras-related C3 botulinum toxin substrate 1 genes (P<0.01 for both treatments). In conclusion, the results of the present study suggested that EPA and pitavastatin are able to prevent atrial electrical remodeling, thrombotic states and oxidative stress in rapidly-paced murine atria.

Eicosapentaenoic Acid Rescues L-Type Ca²⁺ Channel Remodeling Caused by Saturated Fatty Acids via Both Free Fatty Acid Receptor 4-Dependent and -Independent Pathways in Cardiomyocytes

“…These observations suggest that PUFAs may act as antiarrhythmic nutrients to modify cardiac excitability when applied for long-term periods as well. Actually, several independent studies have reported effects of PUFAs to modulate expressions of ion channels in the heart; EPA suppressed expression levels of K + channels and their related genes, Kir6.2, Kcna5, Kcnd2, KChIP2 [47,48], and Na + channel mRNA [49]. Interestingly, in partially agreement with our findings, Xu at al.…”

The Various Roles of Fatty Acids

“…A diet rich in ω3 has since long been connected with maintaining cardiac and vascular health and preventing atherosclerosis [ 202 , 203 , 204 ]. Although some gaps in knowledge remain regarding the precise mode of action explaining the cardioprotective effects of EPA and DHA, several mechanisms have been proposed: preventing arrhythmias [ 205 , 206 ], lowering plasma triacylglycerol [ 207 ], preventing chronic intermittent hypoxia-induced atherosclerosis [ 208 ], decreasing arterial cholesterol delivery and preventing the formation of atherosclerotic plaques in arteries [ 209 ], regulating vascular endothelial cell function and improving vascular relaxation [ 210 ], decreasing platelet aggregation [ 211 ] and arterial inflammatory responses [ 212 ].…”

Filamentation initiated by Cas2 and its association with the acquisition process in cells

“…The clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein (CRISPR-Cas) adaptive immune system is widespread in bacteria and archaea. 1–4 The system was detected in a panel of oral pathogens, including the major oral pathogens Streptococcus mutants 5,6 for caries, Porphyromonas gingivalis 7 for periodontal disease, and Enterococcus faecalis 8,9 for endodontis. The CRISPR-Cas system may play a critical role in microflora and oral health.…”

“…10–12 The CRISPR-Cas system was associated with the pathogenic potential of endodontic oral microbes as well as the status of drug resistance. 8,9…”