标题：Up-regulated ATP-sensitive potassium channels play a role in increased inflammation and plaque vulnerability in macrophages
作者：Ling, Ming-Ying; Ma, Zhi-Yong; Wang, Yuan-Yuan; Qi, Jia; Liu, Lin; Li, Li; Zhang, Yun
作者机构：[Li, Li] Shandong Univ, QiLu Hosp, Key Lab Cardiovas Remodeling & Funct Res, Chinese Minist Educ,Dept Cardiol, Jinan 250012, Peoples R China.; Shand 更多
通讯作者地址：[Li, L]Shandong Univ, QiLu Hosp, Key Lab Cardiovas Remodeling & Funct Res, Chinese Minist Educ,Dept Cardiol, W Wenhua Rd 107, Jinan 250012, Peoples R 更多
关键词：Atherosclerosis; Apolipoprotein E-null mice; ATP-sensitive potassium; channels; Glibenclamide; Inflammation; Macrophages; Transcription factor; NF-kappa B
摘要：Objective: Ion channels expressed in monocytes/macrophages have been tightly attached to atherosclerosis by coupling cellular function with electrical activity. However, the function of ATP-sensitive potassium channels (K-ATP) in atherosclerosis has not been investigated directly. This study was performed to explore its role in atherosclerosis.; Methods and results: ApoE(-/-) mice with collar placement and Ad5-CMV. p53 or lac Z gene transfer with or without intragastric administration glibenclamide were applied to establish the progressive atherosclerosis at different time points and detect the function of K-ATP channel in atherosclerosis. The expression and distribution of K-ATP subunits in plaques were examined and a correlation between K-ATP subunits expressed in macrophages, mainly Kir6.2 and SUR2A, and the vulnerability index of plaques was observed. In vitro, glibenclamide and pinacidil were used to detect the function and mechanism of K-ATP channels in RAW264.7 cells stimulated by LPS. And the data showed that glibenclamide could ameliorate the progress of atherosclerosis and reduce the production of inflammatory cytokines as well as the phosphorylation of p65 and ERK1/2, while inhibitors of p65 leaded to robust expression of K-ATP subunits in macrophages.; Conclusions: We concluded that K-ATP channels in monocytes/macrophages were up-regulated and correlated with increased inflammation in vulnerable plaques, while glibenclamide could rescue the progression. K-ATP channels may stimulate inflammatory reaction by MAPKs/NF-kappa B pathways in macrophages. (C) 2012 Elsevier Ireland Ltd. All rights reserved.