Ewart Marie-Ann, Kohlhaas Christine F, Salt Ian P
Henry Wellcome Laboratory for Cell Biology, Division of Molecular and Cellular Biology, Faculty of Biomedical and Life Sciences, Davidson Building, University of Glasgow, Glasgow G12 8QQ, UK.
Arterioscler Thromb Vasc Biol. 2008 Dec;28(12):2255-7. doi: 10.1161/ATVBAHA.108.175919. Epub 2008 Sep 18.
Proatherosclerotic adhesion of leukocytes to the endothelium is attenuated by NO. As AMP-activated protein kinase (AMPK) regulates endothelial NO synthesis, we investigated the modulation of adhesion to cultured human aortic endothelial cells (HAECs) by AMPK.
HAECs incubated with the AMPK activator, AICAR, or expressing constitutively active AMPK demonstrated reduced TNFalpha-stimulated adhesion of promonocytic U-937 cells. Rapid inhibition of TNFalpha-stimulated U-937 cell adhesion by AICAR was NO-dependent, associated with unaltered cell surface adhesion molecule expression, and reduced MCP-1 secretion by HAECs. In contrast, inhibition of TNFalpha-stimulated U-937 cell adhesion by prolonged AMPK activation was NO-independent and associated with reduced cell surface adhesion molecule expression.
AMPK activation in HAECs inhibits TNFalpha-stimulated leukocyte adhesion by a rapid NO-dependent mechanism associated with reduced MCP-1 secretion and a late NO-independent mechanism whereby adhesion molecule expression, in particular E-selectin, is suppressed.
一氧化氮（NO）可减弱动脉粥样硬化前期白细胞与内皮细胞的黏附。由于AMP激活的蛋白激酶（AMPK）调节内皮细胞NO的合成，我们研究了AMPK对培养的人主动脉内皮细胞（HAECs）黏附的调节作用。
用AMPK激活剂AICAR孵育的HAECs或表达组成型活性AMPK的HAECs，单核细胞U-937细胞受肿瘤坏死因子α（TNFα）刺激后的黏附减少。AICAR对TNFα刺激的U-937细胞黏附的快速抑制作用依赖于NO，与细胞表面黏附分子表达未改变相关，并减少了HAECs分泌单核细胞趋化蛋白-1（MCP-1）。相反，通过延长AMPK激活对TNFα刺激的U-937细胞黏附的抑制作用不依赖于NO，并与细胞表面黏附分子表达减少相关。
HAECs中AMPK的激活通过与MCP-1分泌减少相关的快速NO依赖机制和后期NO非依赖机制（抑制黏附分子表达，特别是E-选择素）来抑制TNFα刺激的白细胞黏附。
