TY - JOUR
T1 - Diabetes adversely affects phospholipid profiles in human carotid artery endarterectomy plaques
AU - Zayed, Mohamed A.
AU - Hsu, Fong Fu
AU - Patterson, Bruce W.
AU - Yan, Yan
AU - Naim, Uzma
AU - Darwesh, Malik
AU - De Silva, Gayan
AU - Yang, Chao
AU - Semenkovich, Clay F.
N1 - Funding Information:
This work was supported by the Vascular Cures Foundation Wylie Scholar Award (M.A.Z.); the Society for Vascular Surgery Foundation Research Seed Grant (M.A.Z.); Washington University Diabetes Research Center’s National Institute of Diabetes and Digestive and Kidney Diseases Grants P30 DK020589 (M.A.Z.) and DK101392 (C.F.S.) and National Heart, Lung, and Blood Institute Grant K08 HL132060 (M.A.Z.); Washington University Mass Spectrometry Center’s National Institutes of Health Service Grants P41 GM103422 and P60 DK20579 (F-F.H.); and Washington University Nutrition Obesity Research Center’s National Institute of Diabetes and Digestive and Kidney Diseases Grant P30 DK056341 (B.W.P.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Author’s Choice—Final version free via Creative Commons CC-BY license. Manuscript received 4 October 2017 and in revised form 21 February 2018. Published, JLR Papers in Press, February 24, 2018 DOI https://doi.org/10.1194/jlr.M081026
Funding Information:
This work was supported by the Vascular Cures Foundation Wylie Scholar Award (M.A.Z.); the Society for Vascular Surgery Foundation Research Seed Grant (M.A.Z.); Washington University Diabetes Research Center’s National Institute of Diabetes and Digestive and Kidney Diseases Grants P30 DK020589 (M.A.Z.) and DK101392 (C.F.S.) and National Heart, Lung, and Blood Institute Grant K08 HL132060 (M.A.Z.); Washington University Mass Spectrometry Center’s National Institutes of Health Service Grants P41 GM103422 and P60 DK20579 (F-F.H.); and Washington University Nutrition Obesity Research Center’s National Institute of Diabetes and Digestive and Kidney Diseases Grant P30 DK056341 (B.W.P.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2018 American Society for Biochemistry and Molecular Biology Inc. All Rights Reserved.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85045017702&partnerID=8YFLogxK
U2 - 10.1194/jlr.M081026
DO - 10.1194/jlr.M081026
M3 - Article
C2 - 29478028
AN - SCOPUS:85045017702
SN - 0022-2275
VL - 59
SP - 730
EP - 738
JO - Journal of lipid research
JF - Journal of lipid research
IS - 4
ER -