出版社：American Society for Biochemistry and Molecular Biology
摘要：Group IIA secretory phospholipase A2 (sPLA2) is an acute-phase protein mediating decreased plasma HDL cholesterol and increased atherosclerosis. This study investigated the impact of macrophage-specific sPLA2 overexpression on lipoprotein metabolism and atherogenesis. Macrophages from sPLA2 transgenic mice have 2.5 times increased rates of LDL oxidation (thiobarbituric acid-reactive substances formation) in vitro (59 ± 5 vs. 24 ± 4 nmol malondialdehyde/mg protein; P −/−) mice were transplanted with bone marrow from either sPLA2 transgenic mice (sPLA2 → LDLR−/−; n = 19) or wild-type C57BL/6 littermates (C57 BL/6 → LDLR−/−; n = 19) and maintained for 8 weeks on chow and then for 9 weeks on a Western-type diet. Plasma sPLA2 activity and plasma lipoprotein profiles were not significantly different between sPLA2 → LDLR−/− and C57BL/6 → LDLR−/− mice. Aortic root atherosclerosis was increased by 57% in sPLA2 → LDLR−/− mice compared with C57BL/6 → LDLR−/− controls ( P iso -iPF2α-VI and aortic levels of 12/15-LO reaction products were each significantly higher ( P 2 → LDLR−/− compared with C57BL/6 → LDLR−/− mice, indicating significantly increased in vivo oxidative stress in sPLA2 → LDLR−/−. These data demonstrate that macrophage-specific overexpression of human sPLA2 increases atherogenesis by directly modulating foam cell formation and in vivo oxidative stress without any effect on systemic sPLA2 activity and lipoprotein metabolism.
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