PS-B02-15: LIGHT POLLUTION, OBESITY, AND HYPERTENSION- “LIFESTYLE” RISK FACTORS ASSOCIATED WITH AN INCREASED RISK OF MALIGNANT ARRHYTHMIAS. ANTIARRHYTHMIC EFFECT OF OMACOR.

Abstract

Objective: Light pollution disrupts circadian rhythms that may promote obesity and hypertension, but their association with the susceptibility to malignant cardiac arrhythmias is not well known. We examined whether continuous light as well as a high sucrose diet affect rat heart gene transcripts, miRNAs, or protein expression and hence arrhythmogenesis. In parallel, the benefit of omega-3 (Omacor) supplementation was assessed. Design and method: In the first experiment, male and female spontaneously hypertensive (SHR) and normotensive Wistar (WR) rats were housed in 12 h/12 h light/dark cycles or exposed to continuous light at 300 lux for 6 weeks. In the second experiment, aged female WR rats were fed with 30% sucrose for 8 weeks. In both experiments half of the rats were supplemented with Omacor (200 mg /100 g b.w). Susceptibility to electrically-inducible ventricular fibrillation (VF) was assessed in perfused heart. Results: Rats exposed to continuous light or fed by sucrose were more vulnerable to develop VF. There was a down-regulation of myocardial connexin-43 (Cx43) along with an increased pro-inflammatory NF-kB and iNOS transcripts and decreased sarcoplasmic reticulum Ca2+ ATPase transcripts in response to continuous light. Omacor treatment increased the electrical threshold for VF induction associated with attenuation of pro-arrhythmic alterations in myocardial Cx43, NF-kB and iNOS. Sucrose fed rats exhibited suppression of Cx43 and PKC epsilon signaling, along with upregulation of myocardial PKC delta and miR-30a that is involved in fibrosis. Myocardial miR-1 expression levels involved in the regulation of Cx43 were not affected by the sucrose diet nor Omacor treatment. Antiarrhythmic effects of Omacor supplementation have been shown by attenuation of Cx43, PKC, and miR-30a myocardial abnormalities. Conclusions: Findings suggest that light pollution and sucrose diet jeopardize myocardial Cx43-mediated electrical communication, thereby increase susceptibility of the heart to malignant arrhythmias. Adverse effects were alleviated by treatment with Omacor, supporting its potential benefit and the relevance of monitoring the omega-3 index in at-risk human populations. This research was supported by VEGA 2/0002/20, 2/0158/19, APVV 21-0410, 18-0548, 19-0317, EU ITMS 26230120009