Abstract 218: Omega-3 Fatty Acid Supplement Prevents Progression of Intracranial Atherosclerosis

Abstract

Introduction: Intracranial atherosclerotic stenosis (ICAS) is a disease state that has been implicated as a leading cause of recurrent ischemic stroke. While popular media has promoted the use of omega-3 fatty acid (OFA) supplementation for its purported health benefits, few studies have looked at the molecular mechanisms at play within the cerebral vasculature. We adapted a rat model for atherosclerosis and applied it to the brain, for the first time to our knowledge, to study intracranial atherosclerosis (ICA). In this study we investigated the hypothesis that dietary supplementation of OFA attenuated the progression of ICA. Methods: Twelve week old male Sprague-Dawly rats were placed on a 1% cholesterol diet. During the first two weeks, NG-nitro-L-arginine methyl ester (L-NAME, 3 mg/mL) was added to their drinking water to induce intimal changes making the rats susceptible to atherosclerosis. One group of rats had their diet supplemented with OFA (5mg/kg/day). Animals were sacrificed at three, six of supplementation. Histological sections of the brains were made to study middle cerebral artery (MCA) morphometry and intimal thickening was quantified by measuring lumen and vessel wall areas. Additionally at each time point blood lipids and glucose were measured before animal sacrifice. Results: The rats subjected to the high cholesterol diet and L-NAME administration displayed blood markers of atherosclerosis which became more severe in time. The levels of LDL, glucose, cholesterol, and triglycerides were significantly elevated compared to control. In the OFA treatment group, these biomarkers were dramatically attenuated. Furthermore, while the atherogenic treatment led to stenosis of the lumen and intimal thickening in the MCA, dietary OFA prevented these characteristic morphological changes, in which the infiltration of the vessel walls by macrophages was observed, supporting the antiatherogenic nature of this treatment. Conclusions: Long term dietary supplementation with OFA thwarts the development of ICA. It prevents the infiltration of the vessel walls by macrophages thus reducing inflammation and intimal thickening. Omega-3 fatty acids are an inexpensive and widely available dietary supplement which shows promise in preventing ICAS.