Diabetes adversely affects phospholipid profiles in human carotid artery endarterectomy plaques

Chao Yang,Yan Yan,Gayan De Silva,Mohamed A Zayed,Fong-Fu Hsu,Bruce W Patterson,Uzma Naim,Malik Darwesh,Clay F Semenkovich

doi:10.1194/jlr.m081026

Abstract

Patients with diabetes are at higher risk of developing carotid artery stenosis and resultant stroke. Arachidonoyl phospholipids affect plaque inflammation and vulnerability, but whether diabetic patients have unique carotid artery phospholipidomic profiles is unknown. We performed a comprehensive paired analysis of phospholipids in extracranial carotid endarterectomy (CEA) plaques of matched diabetic and nondiabetic patients and analyzed mass spectrometry-derived profiles of three phospholipids, plasmenyl-phosphatidylethanolamine (pPE), phosphatidylserine (PS), and phosphatidylinositol (PI), in maximally (MAX) and minimally (MIN) diseased CEA segments. We also measured levels of arachidonic acid (AA), produced by pPE hydrolysis, and choline-ethanolamine phosphotransferase 1 (CEPT1), responsible for most pPE de novo biosynthesis. In paired analysis, MIN CEA segments had higher levels than MAX segments of pPE (P < 0.001), PS (P < 0.001), and PI (P < 0.03). MIN diabetic plaques contained higher levels than MAX diabetic plaques of arachidonoyl pPE38:4 and pPE38:5 and CEPT1 was upregulated in diabetic versus nondiabetic plaques. AA levels were relatively greater in MIN versus MAX segments of all CEA segments, and were higher in diabetic than nondiabetic plaques. Our findings suggest that arachidonoyl phospholipids are more likely to be abundant in the extracranial carotid artery plaque of diabetic rather than nondiabetic patients.

Highlights

Patients with diabetes are at higher risk of developing carotid artery stenosis and resultant stroke
To determine whether choline-ethanolamine phosphotransferase 1 (CEPT1) is altered in the carotid arteries of diabetic human subjects, we evaluated carotid endarterectomy (CEA) plaques (Fig. 1A, B) of 17 subjects and observed a 53% increase in CEPT1 protein expression in diabetic specimens (P < 0.05; Fig. 1C)
Because the content of both arachidonoyl pPEs and cytosolic phospholipase A2 (cPLA2) levels in CEA plaque appeared to be altered relative to disease severity and the presence of diabetes, we explored whether arachidonic acid (AA) content was different between MIN and MAX diseased CEA segments

Summary

Introduction

Patients with diabetes are at higher risk of developing carotid artery stenosis and resultant stroke. Arachidonoyl phospholipids affect plaque inflammation and vulnerability, but whether diabetic patients have unique carotid artery phospholipidomic profiles is unknown. We performed a comprehensive paired analysis of phospholipids in extracranial carotid endarterectomy (CEA) plaques of matched diabetic and nondiabetic patients and analyzed mass spectrometry-derived profiles of three phospholipids, plasmenyl-phosphatidylethanolamine (pPE), phosphatidylserine (PS), and phosphatidylinositol (PI), in maximally (MAX) and minimally (MIN) diseased CEA segments. MIN diabetic plaques contained higher levels than MAX diabetic plaques of arachidonoyl pPE38:4 and pPE38:5 and CEPT1 was upregulated in diabetic versus nondiabetic plaques. AA levels were relatively greater in MIN versus MAX segments of all CEA segments, and were higher in diabetic than nondiabetic plaques. Our findings suggest that arachidonoyl phospholipids are more likely to be abundant in the extracranial carotid artery plaque of diabetic rather than nondiabetic patients.—Zayed, M. In the majority of mammalian tissue, the final step of PE synthesis is catalyzed by the essential enzyme, choline-ethanolamine phosphotransferase

Methods

Results

Conclusion