出版社：American Society for Biochemistry and Molecular Biology
摘要：Myeloperoxidase (MPO) is an oxidant-generating enzyme presentin macrophages at atherosclerotic lesions and implicated incoronary artery disease (CAD). Although mouse models are importantfor investigating the role of MPO in atherosclerosis, neithermouse MPO nor its oxidation products are detected in lesionsin murine models. To circumvent this problem, we generated transgenicmice expressing two functionally different human MPO alleles,with either G or A at position –463, and crossed theseto the LDL receptor-deficient (LDLR–/–) mouse. The–463G allele is linked to higher MPO expression and increasedCAD incidence in humans. Both MPO alleles were expressed ina subset of lesions in high-fat-fed LDLR–/– mice,notably at necrotic lesions with cholesterol clefts. MPOG-expressingLDLR–/– males (but not females) developed significantlyhigher serum cholesterol, triglycerides, and glucose, all correlatingwith increased weight gain/obesity, implicating MPO in lipidhomeostasis. The MPOG- and MPOA-expressing LDLR–/–males also exhibited significantly larger aortic lesions thancontrol LDLR–/– males. The human MPO transgenicmodel will facilitate studies of MPO involvement in atherosclerosisand lipid homeostasis.Supplementary key words myeloperoxidase • atherosclerosis • hyperlipidemia • cholesterol • triglycerides • macrophage
