Abstract P2095: Role Of Intraplaque Lipids In Atherosclerotic Plaque Vulnerability

Abstract

Background: Hyperlipidemia plays a pivotal role in the pathogenesis of diabetes, atherosclerosis, and cardiovascular diseases. Specific lipids of atherosclerotic plaques are potentially one of the local factors which render them susceptible to rupture. Their underlying unresolved inflammation and oxidative stress contribute to the transition from stable to unstable plaques. Therefore, we aimed to identify, characterize, and compare the intraplaque lipids composition among diabetic and non-diabetic patients and to ascertain their role in inflammation, and atherosclerotic plaque destabilization and rupture. Methods: Approved by the IRB, University of Arizona, Tucson Lipids were analyzed by liquid chromatography-mass spectrometry (LC-MS) from 40 surgically removed endarterectomy specimens that include Asymptomatic & Non-diabetic (n=13), Symptomatic & Non-diabetic (n=17), Asymptomatic & Diabetic (n=5) iv. Symptomatic & Diabetic (n=5) patients. Seventy nine lipid species from the main lipid classes phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylethanolamine (PE), phosphatidylinositol (PI), cholesteryl ester (CE) phosphatidylglycerol (PG), sphingomyelin (SM), and ceramide (Cer) were included in this lipidomic profiling. Results: LC-MS data analysis identified a significant difference (p<0.05) in 2 individual lipid species – a long chain polyunsaturated PC(40:7) and SM(18:1) between diabetic and non-diabetic (Table:1). A total of 23 lipid species were significantly (p<0.05 to p<0.005) differentially present between symptomatic and asymptomatic samples. Symptomatic diabetic and nondiabetic samples showed a significant (p<0.05 to p<0.005) difference in 13 lipids belonging to PC, SM and PE. Our studies also showed a higher peroxidation of intraplaque lipid from diabetic patients compared to non-diabetics, and a significant increase in reactive oxygen species (ROS) production in human coronary artery smooth muscle cells treated with lipids from diabetic plaques. Conclusions: This exploratory analysis showed distinct patterns of intraplaque lipid composition. Identification of these high-risk plaque lipid biomarkers will help to delineate the cellular and molecular mechanism responsible for stable to vulnerable plaques transition.