Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Department of Cardiology, QiLu Hospital, Shandong University, West Wenhua Road 107, Jinan 250012, PR China.
Atherosclerosis. 2013 Feb;226(2):348-55. doi: 10.1016/j.atherosclerosis.2012.11.016. Epub 2012 Nov 23.
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.
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.
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-κB pathways in macrophages.
在单核细胞/巨噬细胞中表达的离子通道通过将细胞功能与电活动偶联，与动脉粥样硬化紧密相连。然而，ATP 敏感性钾通道（K（ATP））在动脉粥样硬化中的功能尚未被直接研究。本研究旨在探索其在动脉粥样硬化中的作用。
应用颈圈放置的 ApoE（-/-）小鼠和 Ad5-CMV.p53 或 lac Z 基因转移，同时或不给予格列本脲进行胃内给药，以在不同时间点建立进行性动脉粥样硬化，并检测动脉粥样硬化中 K（ATP）通道的功能。检测斑块中 K（ATP）亚基的表达和分布，并观察巨噬细胞中 K（ATP）亚基（主要是 Kir6.2 和 SUR2A）的表达与斑块易损性指数之间的相关性。在体外，使用格列本脲和吡那地尔检测 LPS 刺激的 RAW264.7 细胞中 K（ATP）通道的功能和机制。结果表明，格列本脲可以改善动脉粥样硬化的进展，减少炎症细胞因子的产生以及 p65 和 ERK1/2 的磷酸化，而 p65 的抑制剂则导致巨噬细胞中 K（ATP）亚基的表达明显增加。
我们得出结论，单核细胞/巨噬细胞中的 K（ATP）通道上调，并与易损斑块中炎症的增加相关，而格列本脲可以挽救其进展。K（ATP）通道可能通过 MAPKs/NF-κB 通路刺激巨噬细胞中的炎症反应。
