标题：High-level lipoprotein [a] expression in transgenic mice: evidence for oxidized phospholipids in lipoprotein [a] but not in low density lipoproteins
出版社：American Society for Biochemistry and Molecular Biology
摘要：Efforts to elucidate the role of lipoprotein [a] (Lp[a]) inatherogenesis have been hampered by the lack of an animal modelwith high plasma Lp[a] levels. We produced two lines of transgenicmice expressing apolipoprotein [a] (apo[a]) in the liver andcrossed them with mice expressing human apolipoprotein B-100(apoB-100), generating two lines of Lp[a] mice. One had Lp[a]levels of 700 mg/dl, well above the 30 mg/dl threshold associatedwith increased risk of atherosclerosis in humans; the otherhad levels of 35 mg/dl. Most of the LDL in mice with high-levelapo[a] expression was covalently bound to apo[a], but most ofthe LDL in the low-expressing line was free. Using an enzyme-linkedsandwich assay with monoclonal antibody EO6, we found high levelsof oxidized phospholipids in Lp[a] from high-expressing micebut not in LDL from low-expressing mice or in LDL from humanapoB-100 transgenic mice (P < 0.00001), even though all micehad similar plasma levels of human apoB-100.
The increase in oxidized lipids specific to Lp[a] in high-levelapo[a]-expressing mice suggests a mechanism by which increasedcirculating levels of Lp[a] could contribute to atherogenesis.Abbreviations: apo[a], apolipoprotein [a]; apoB-100, apolipoprotein B-100; FPLC, fast-performance liquid chromatography; IDL, intermediate density lipoprotein; Lp[a], lipoprotein [a]; MAb, monoclonal antibody; OxLDL, oxidized low density lipoprotein; RLU, relative light units
Supplementary key words atherosclerosis • oxidized low density lipoprotein • apolipoprotein [a] • cardiovascular • apolipoprotein B-100
700 mg/dl, well above the 30 mg/dl threshold associated with increased risk of atherosclerosis in humans; the other had levels of 
