Detection and biological activities of carboxyethylpyrrole ethanolamine phospholipids (CEP-EPs).
Oxidation of docosahexaenoate phospholipids produces 4-hydroxy-7-oxo-hept-5-eonyl phospholipids (HOHA-PLs) that react with protein lysyl ε-amino residues to generate 2-ω-carboxyethylpyrrole (CEP) derivatives, endogenous factors that induce angiogenesis in the retina and tumors. It seemed likely, but remained unproven, that HOHA-PLs react with ethanolamine phospholipids (EPs) in vivo to generate CEP-EPs. We now show that CEP-EPs are present in human blood at 4.6-fold higher levels in age-related macular degeneration plasma than in normal plasma. We also show that CEP-EPs are pro-angiogenic, inducing tube formation by human umbilical vein endothelial cells by activating Toll-like receptor 2. CEP-EP levels may be a useful biomarker for clinical assessment of AMD risk and CEP-associated tumor progression and a tool for monitoring the efficacy of therapeutic interventions.
Department of Chemistry, Case Western Reserve University , Cleveland, Ohio 44106, United States.
Hua
H
Wang
Junhong
J
Guo
Xiaoxia Z
XZ
West
Hemant K
HK
Bid
Liang
L
Lu
Li
L
Hong
Geeng-Fu
GF
Jang
Lei
L
Zhang
John W
JW
Crabb
Mikhail
M
Linetsky
Robert G
RG
Salomon
D002853:Chromatography, Liquid; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008268:Macular Degeneration / Q000097:blood; D009682:Magnetic Resonance Spectroscopy; D010714:Phosphatidylethanolamines / Q000097:blood*; D010743:Phospholipids / Q000097:blood* / Q000502:physiology; D053719:Tandem Mass Spectrometry
D010714:Phosphatidylethanolamines; D010743:Phospholipids; C483858:phosphatidylethanolamine