title: Mouse plasminogen has oxidized phosphatidylcholine adducts that are not metabolized by lipoprotein-associated phospholipase A₂under basal conditions.
abstract: We previously showed that plasminogen (Plg) isolated from the plasma of normal human subjects contains 1-2 moles of oxidized phosphatidylcholine (oxPtdPC) adducts/mole of protein. Moreover, we suggested that these species are generated at the hepatic site and speculated that they may play a role in the reported cardiovascular pathogenicity of Plg. We aimed to determine whether mouse Plg also harbors linked oxPtdPCs and whether these molecules are metabolized by lipoprotein-associated phospholipase A(2)/PAF acetylhydrolase (Lp-PLA(2)/PAF-AH), an enzyme specific for hydrolysis of oxPtdPCs. We determined the total concentration of Plg in plasma samples from control (WT) and Lp-PLA(2)-deficient (KO) mice, we isolated Plg, and assessed its content of oxPtdPCs by immunoblot analyses. We also evaluated whether human recombinant Lp-PLA(2) metabolized Plg-linked oxPtdPCs in vivo and in vitro. WT and KO mice expressed comparable levels (14.4-15.8 mg/dL) of plasma Plg, as determined by ELISA. We observed no differences in the content of oxPtdPC in Plg isolated from the two mouse strains and in parallel no changes in oxPtdPC content in mouse Plg following incubation with pure recombinant Lp-PLA(2). Plg from mouse plasma contains oxPtdPC adducts that are not affected by the action of Lp-PLA(2), suggesting that linkage to Plg protects oxPtdPCs from metabolism during their transport in the plasma. This modification may have important physio-pathological implications related to the function of Plg, oxPtdPCs, or both.
authors: Department of Medicine, University of Chicago, Chicago, IL 60637, USA; E-Mails: celina@medicine.bsd.uchicago.edu (C.E.); dpfaffin@medicine.bsd.uchicago.edu (D.P.).
authors: Celina
authors: C
authors: Edelstein
authors: Ditta
authors: D
authors: Pfaffinger
authors: Ethan C
authors: EC
authors: Reichert
authors: Diana M
authors: DM
authors: Stafforini
authors: Angelo M
authors: AM
authors: Scanu
references: Biochim Biophys Acta. 2010 Jul;1801(7):738-45
references: 20346413
references: Circulation. 2001 May 22;103(20):2495-500
references: 11369691
references: J Lipid Res. 2005 Apr;46(4):769-78
references: 15654123
references: J Biol Chem. 2003 Dec 26;278(52):52841-7
references: 14557258
references: FASEB J. 2009 Mar;23(3):950-6
references: 19001055
references: Science. 1970 Dec 4;170(3962):1095-6
references: 5475635
references: FASEB J. 2000 Oct;14(13):2032-9
references: 11023987
references: Can J Biochem Physiol. 1959 Aug;37(8):911-7
references: 13671378
references: J Lipid Res. 2010 Oct;51(10):2967-75
references: 20584868
references: J Biol Chem. 2008 Mar 7;283(10):6428-37
references: 18165686
references: Biochim Biophys Acta. 2006 Nov;1761(11):1359-72
references: 17049457
references: Pediatr Res. 2010 Sep;68(3):225-30
references: 20531249
references: Trends Cardiovasc Med. 2004 Jul;14(5):180-6
references: 15261889
references: Curr Opin Lipidol. 2008 Aug;19(4):369-77
references: 18607184
references: Cardiovasc Drugs Ther. 2009 Feb;23(1):73-83
references: 18949548