Effect of endothelial cell CaMKII activation on atherosclerosis in mice

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Objective To investigate the effect of oxidative stress-induced CaMKⅡ activation in endothelial cells on atherosclerosis and its mechanism. Methods Human umbilical vein endothelial cells (HUVECs) were cultured in vitro and divided into the control group, H2O2 group, H2O2+KN93 group, and H2O2+KN92 group. The ROS level, cell viability, migration ability, and adhesion ability were determined, and the function of endothelial cells was assessed. RT-PCR was used to determine the expression levels of CaMKⅡ, p-CaMKⅡ, ox-CaMKⅡ, notch-1, NF-κB-p65 and VCAM-1. Thirty 8-week-old male ApoE (-/-) mice were randomly divided into 3 groups: the high-fat diet group (n=10) received high-fat diet and intraperitoneal injection of DMSO; the high-fat diet+KN93 group (n=10) received high-fat diet and intraperitoneal injection of KN93 (10 mg-1·kg-1·d-1) ; and the high-fat diet+KN92 group (n=10) received high-fat diet and intraperitoneal injection of KN92 (10 mg-1·kg-1·d-1) . The body weight and blood lipid level in each group were recorded. The oil Red O staining of the aorta was performed. The aortic root plaque area and aortic lipid deposition were compared between the groups. Results Compared with the H2O2+KN92 group and H2O2 group, the endothelial cell viability, migration ability, and adhesion ability in the H2O2+KN93 group were all improved (P 0.05) . Conclusion KN93 may ameliorate the endothelial dysfunction through the CaMKⅡ/notch-1/NF-κB-p65/VCAM-1 pathway, and thereby delay the occurrence and development of atherosclerosis. Key words: Oxidative stress; Atherosclerosis; Endothelial cell dysfunction; CaMKⅡ