Absence of Myeloid COX-2 Attenuates Acute Inflammation but Does Not Influence Development of Atherosclerosis in Apolipoprotein E Null Mice
Absence of Myeloid COX-2 Attenuates Acute Inflammation but Does Not Influence Development of Atherosclerosis in Apolipoprotein E Null Mice
复制标题
DOI：
10.1161/atvbaha.109.198762
复制
发表时间：
2010-02-01
影响因子：
8.7
通讯作者：
Reddy, Srinivasa T.
中科院分区：
文献类型：
--
作者：
Narasimha, Ajay J.;Watanabe, Junji;Reddy, Srinivasa T.
目的-骨髓细胞环氧合酶-2 (COX-2) 在动脉粥样硬化进展中的作用尚未明确定义。方法和结果-我们使用骨髓特异性 COX-2(-/-) (COX-2(-M/-M)) 小鼠在高脂血症载脂蛋白 (apo) 上研究了骨髓谱系中表达的 COX-2 在动脉粥样硬化发展中的作用E-/- 背景 (COX-2(-M/-M)/apoE(-/-))。骨髓 COX-2 耗竭导致急性炎症显着减弱，与气囊模型中 PGE2 水平降低相对应。与饲喂普通饮食或西方饮食的 apoE(-/-) 同窝小鼠相比，骨髓细胞中 COX-2 的耗竭并不影响 COX-2(-M/-M)/apoE(-/-) 中动脉粥样硬化的发展。骨髓细胞 COX-2 对动脉粥样硬化发展的贡献出人意料地缺乏，这并不是由于骨髓细胞和淋巴细胞群的维持、分化或动员的改变所致。此外，骨髓COX-2耗竭导致COX-2(-M/-M)/apoE(-/-)小鼠的血清前列腺素水平和动脉粥样硬化病变的细胞组成没有改变。结论——我们的结果表明，骨髓细胞（包括巨噬细胞）中COX-2的表达不影响小鼠动脉粥样硬化的发展。 （动脉硬化血栓 Vasc Biol.2010；30：260-268。）
Objective-The role of myeloid cell cyclooxygenase-2 (COX-2) in the progression of atherosclerosis has not been clearly defined.Methods and Results-We investigated the role of COX-2 expressed in the myeloid lineage in the development of atherosclerosis using a myeloid-specific COX-2(-/-) (COX-2(-M/-M)) mouse on a hyperlipidemic apolipoprotein (apo) E-/- background (COX-2(-M/-M)/apoE(-/-)). Myeloid COX-2 depletion resulted in significant attenuation of acute inflammation corresponding with decreased PGE2 levels in an air pouch model. COX-2 depletion in myeloid cells did not influence development of atherosclerosis in COX-2(-M/-M)/apoE(-/-) when compared to apoE(-/-) littermates fed either chow or western diets. The unanticipated lack of contribution of myeloid COX-2 to the development atherosclerosis is not attributable to altered maintenance, differentiation, or mobilization of myeloid and lymphoid populations. Moreover, myeloid COX-2 depletion resulted in unaltered serum prostanoid levels and cellular composition of atherosclerotic lesions of COX-2(-M/-M)/apoE(-/-) mice.Conclusions-Our results suggest that COX-2 expression in myeloid cells, including macrophages, does not influence the development of atherosclerosis in mice. (Arterioscler Thromb Vasc Biol. 2010; 30:260-268.)