Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Calif 90095, USA.
Arterioscler Thromb Vasc Biol. 2010 Feb;30(2):260-8. doi: 10.1161/ATVBAHA.109.198762. Epub 2009 Nov 19.
The role of myeloid cell cyclooxygenase-2 (COX-2) in the progression of atherosclerosis has not been clearly defined.
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 PGE(2) 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.
Our results suggest that COX-2 expression in myeloid cells, including macrophages, does not influence the development of atherosclerosis in mice.
髓样细胞环氧化酶-2（COX-2）在动脉粥样硬化进展中的作用尚未明确。
我们使用载脂蛋白 E（apoE）基因敲除背景下的骨髓特异性 COX-2 敲除（COX-2(-M/-M)）小鼠（COX-2(-M/-M)/apoE(-/-)）研究了髓样细胞中 COX-2 的表达在动脉粥样硬化发生中的作用。在气囊模型中，髓样 COX-2 的耗竭导致急性炎症明显减弱，相应的 PGE（2）水平降低。与喂食标准饮食或普通饮食的 apoE（-/-）同窝仔鼠相比，髓样细胞 COX-2 耗竭并未影响 COX-2(-M/-M)/apoE(-/-)小鼠动脉粥样硬化的发展。出乎意料的是，髓样 COX-2 对动脉粥样硬化发展的贡献缺失不能归因于骨髓和淋巴样细胞群的维持、分化或动员的改变。此外，髓样 COX-2 耗竭并未改变 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。
我们的结果表明，髓样细胞（包括巨噬细胞）中的 COX-2 表达并不影响小鼠动脉粥样硬化的发生。
