Abstract 312: Arterial CEPT1 Expression Correlates With Diabetes and Atherosclerotic Occlusive Disease

Abstract

Choline/ethanolamine phosphotransferase-1 (CEPT1) is a ubiquitously expressed enzyme that catalyzes the final step in synthesis of the majority of mammalian phospholipids, that are known to also impact atheroprogression. We previously found that in the setting of diabetes CEPT1 expression and downstream phospholipid biosynthesis are critically altered in hepatocytes. We therefore hypothesized that in diabetes CEPT1 expression is also altered in arterial tissue, and correlates with disease severity. To test this hypothesis we evaluated CEPT1 protein expression in murine and human arterial tissue in the presence or absence of diabetes, and/or advanced occlusive disease. CEPT1 expression in the aorta of Db/Db mice was 43% increased relative to Wt controls (n=7 per mouse group;p=0.03). On the other hand, CEPT1 expression was not significantly altered in Db/Db myocardial or skeletal muscle (p=0.2 and p=0.09, respectively). To determine whether our findings translate to similar CEPT1 expression patterns in human arterial tissue, we harvested carotid artery intima from 11 diabetic and 7 non-diabetic patients undergoing carotid endarterectomy (CEA). We also harvested peripheral arterial segments with minimal and maximal atherosclerotic occlusive disease from 8 diabetic and 4 non-diabetic patients undergoing lower extremity amputation. Relative to non-diabetic patients, patients who were diabetic had increased CEPT1 expression in CEA tissue (53% increase;p=0.05), and peripheral arterial segments (36% increase;p=0.04). Interestingly, relative to peripheral arteries with minimal atherosclerotic occlusive disease, segments with maximal disease had a two-fold increase in CEPT1 expression (p<0.01). Analysis of maximally diseased peripheral arteries demonstrated significantly higher CEPT1 expression among diabetic patients (34% increase;p=0.03). There was no difference in CEPT1 expression in minimally diseased arteries of diabetic and non-diabetic patients (p=0.1). These findings highlight that increased CEPT1 expression correlates with diabetes and extent of arterial occlusive disease. Furthermore, they argue that CEPT1 is a unique arterial tissue biomarker for occlusive disease severity.