Up-regulated ATP-sensitive potassium channels play a role in increased inflammation and plaque vulnerability in macrophages

ObjectiveIon 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 (KATP) in atherosclerosis has not been investigated directly. This study was performed to explore its role in atherosclerosis.Methods and resultsApoE−/− 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 KATP channel in atherosclerosis. The expression and distribution of KATP subunits in plaques were examined and a correlation between KATP 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 KATP 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 KATP subunits in macrophages.ConclusionsWe concluded that KATP channels in monocytes/macrophages were up-regulated and correlated with increased inflammation in vulnerable plaques, while glibenclamide could rescue the progression. KATP channels may stimulate inflammatory reaction by MAPKs/NF-κB pathways in macrophages.

► The expression and distribution of KATP channels in plaques was described. ► Kir6.2 and SUR2A subunits mainly expressed in macrophages. ► KATP channels in macrophages were correlated with vulnerability of plaques. ► The expression of KATP subunits were induced by LPS in RAW264.7 cells. ► KATP channels may stimulate inflammation by MAPKs/NF-κB pathways in macrophages.