Macrophage-expressed group IIA secretory phospholipase A2 increases atherosclerotic lesion formation in LDL receptor-deficient mice.
Macrophage-expressed group IIA secretory phospholipase A2 increases atherosclerotic lesion formation in LDL receptor-deficient mice.
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巨噬细胞表达的 IIA 型分泌性磷脂酶 A2 会增加 LDL 受体缺陷小鼠的动脉粥样硬化病变形成。
DOI：
10.1161/01.atv.0000051701.90972.e5
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
deBeer,FrederickC
中科院分区：
文献类型：
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作者：
Webb,NancyR;Bostrom,MeredithA;Szilvassy,StephenJ;vanderWesthuyzen,DeneysR;Daugherty,Alan;deBeer,FrederickC
Objective—Transgenic mice expressing human group IIA secretory phospholipase A2(group IIA sPLA2) spontaneously develop atherosclerotic lesions. The mechanism for this proatherogenic effect is likely multifactorial, because HDL-cholesterol is significantly lower and LDL/VLDL cholesterol is slightly higher in transgenic mice compared with nontransgenic littermates. In the present study, we show for the first time that elicited peritoneal macrophages from transgenic mice express human group IIA sPLA2. This study tested whether macrophage-expressed sPLA2contributes to atherogenesis.Methods and Results—Bone marrow cells from either sPLA2transgenic mice or control C57BL/6 mice were transplanted into LDL receptor–deficient mice. After hematopoietic engraftment, animals were fed a diet enriched with saturated fat and cholesterol for 12 weeks. Despite a lack of effect on serum lipoprotein concentrations, the presence of bone marrow–derived cells expressing human group IIA sPLA2resulted in a significant increase in the extent of atherosclerosis in the aortic arch (12.8±1.4% versus 7.4±0.9%;P<0.005) and aortic sinus (0.3±0.03 mm2versus 0.2±0.04 mm2;P<0.05).Conclusions—Group IIA sPLA2can contribute to atherosclerotic lesion development through a mechanism that is independent of systemic lipoprotein metabolism.
