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 A2/PAF acetylhydrolase (Lp-PLA2/PAF-AH), an enzyme specific for hydrolysis of oxPtdPCs. We determined the total concentration of Plg in plasma samples from control (WT) and Lp-PLA2-deficient (KO) mice, we isolated Plg, and assessed its content of oxPtdPCs by immunoblot analyses. We also evaluated whether human recombinant Lp-PLA2 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-PLA2. Plg from mouse plasma contains oxPtdPC adducts that are not affected by the action of Lp-PLA2, 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.
Keywords: mouse plasminogen; oxidized phosphatidylcholine; lipoprotein-associated phospholipase A2; oxidized phopholipids
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Edelstein, C.; Pfaffinger, D.; Reichert, E.C.; Stafforini, D.M.; Scanu, A.M. Mouse Plasminogen Has Oxidized Phosphatidylcholine Adducts That Are Not Metabolized by Lipoprotein-Associated Phospholipase A2 under Basal Conditions. Int. J. Mol. Sci. 2010, 11, 5339-5347.
Edelstein C, Pfaffinger D, Reichert EC, Stafforini DM, Scanu AM. Mouse Plasminogen Has Oxidized Phosphatidylcholine Adducts That Are Not Metabolized by Lipoprotein-Associated Phospholipase A2 under Basal Conditions. International Journal of Molecular Sciences. 2010; 11(12):5339-5347.
Edelstein, Celina; Pfaffinger, Ditta; Reichert, Ethan C.; Stafforini, Diana M.; Scanu, Angelo M. 2010. "Mouse Plasminogen Has Oxidized Phosphatidylcholine Adducts That Are Not Metabolized by Lipoprotein-Associated Phospholipase A2 under Basal Conditions." Int. J. Mol. Sci. 11, no. 12: 5339-5347.