Cardioprotective Effect Of Melatonin And Omega-3 Fatty Acids On The Myocardial Electrical Signaling In The Aged Obese Female Rats

Objective: Obesity-associated hypertension and accompanying metabolic consequences of weight gain increase the risk of cardiac arrhythmias and sudden cardiac death. Design and method: We aimed to examine whether high-sucrose intake in aged female rats affects blood pressure, expression of genes and proteins implicated in electrical coupling such as connexin-43 (Cx43), protein kinase C (PKC), miR-1, miR-30a as well as susceptibility of the heart to malignant arrhythmias. Supplementation with cardioprotective compounds, melatonin (40 μg/ml/day) and omega-3 polyunsaturated fatty acids (Omacor, 25 g/kg of rat chow) was observed as well. Results: Intake of 30% sucrose solution for 8 weeks did not increase blood pressure, blood glucose, but increased serum cholesterol, triglycerides, body weight, heart weight, and retroperitoneal adipose tissues. It was accompanied by downregulation of cardiac Cx43 and PKC epsilon signaling along with an upregulation of myocardial PKC delta and miR-30a rendering the heart prone to ventricular arrhythmias. There was a clear benefit of melatonin or omacor supplementation due to their antiarrhythmic effects associated with the attenuation of myocardial Cx43, PKC, and miR-30a abnormalities as well as adiposity. Conclusions: In comparing with other studies, we can conclude that the 8-week ingestion of 30% sucrose solution was not enough to increase blood pressure, which can be attributed to differences in the specific component of high-calorie diet, strain, and sex. We also find that high-sucrose intake impairs myocardial signaling mediated by Cx43 and PKC contributing to increased susceptibility of the older obese female rat hearts to malignant arrhythmias. This work was supported by APVV-15–0119, Slovak Cardiological Society Grant and VEGA 2/0167/15, 2/0076/16, 2/0158/19 grants, and by EU Structural Fund ITMS 26230120006