Vascular Electrical Stimulation with Wireless, Battery‐Free, and Fully Implantable Features Reduces Atherosclerotic Plaque Formation Through Sirt1‐Mediated Autophagy

Abstract

AbstractElectrical stimulation (ES) is a safe and effective procedure in clinical rehabilitation with few adverse effects. However, studies on ES for atherosclerosis (AS) are scarce because ES does not provide a long‐term intervention for chronic disease processes. Battery‐free implants and surgically mounted them in the abdominal aorta of high‐fat‐fed Apolipoprotein E (ApoE−/−) mice are used, which are electrically stimulated for four weeks using a wireless ES device to observe changes in atherosclerotic plaques. Results showed that there is almost no growth of atherosclerotic plaque at the stimulated site in AopE−/− mice after ES. RNA‐sequencing (RNA‐seq) analysis of Thp‐1 macrophages reveal that the transcriptional activity of autophagy‐related genes increase substantially after ES. Additionally, ES reduces lipid accumulation in macrophages by restoring ABCA1‐ and ABCG1‐mediated cholesterol efflux. Mechanistically, it is demonstrated that ES reduced lipid accumulation through Sirtuin 1 (Sirt1)/Autophagy related 5 (Atg5) pathway‐mediated autophagy. Furthermore, ES reverse autophagic dysfunction in macrophages of AopE−/− mouse plaques by restoring Sirt1, blunting P62 accumulation, and inhibiting the secretion of interleukin (IL)‐6, resulting in the alleviation of atherosclerotic lesion formation. Here, a novel approach is shown in which ES can be used as a promising therapeutic strategy for AS treatment through Sirt1/Atg5 pathway‐mediated autophagy.