To investigate the effort of mitochondrial calcium transport and calcium-induced membrane permeability transition in alleviating atherosclerosis. The experimental mice were divided into three groups: the control group (C57BL/6 mice with normal diet), the atherosclerosis group (apolipoprotein E-deficient (ApoE−/−) mice with high-fat diet) and the mitochondrial targeting agent group (ApoE−/− mouse with high-fat diet). The mean fluorescence intensity of Ca2+ in the atherosclerosis group is significantly higher than control group and mitochondrial targeting agent group. But the mean fluorescence intensity of Ca2+-ATPase is lower than other groups. The macrophage recruitment (F4/80 positive area) and the expression of tumor necrosis factor alpha, interleukin-6, pyrin domain containing protein 3, intercellular cell adhesion molecule-1, p38 mitogen-activated protein kinase and Jun kinase 1/2 phosphorylation in the atherosclerosis group are higher that other groups. Treatment with mitochondrial targeting agents reduced the levels of elevated cyt C and cleaved caspase-3 in atherosclerotic mice (p<0.05). Mitochondrial targeting agents interfere with mitochondrial calcium transport and calcium-induced membrane permeability transition, inhibit MAPK/JNK pathway activation, inhibit foam cell formation and alleviate the process of atherosclerosis.
- endothelial cells
Data availability statement
Data are available upon reasonable request.
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Contributors SC, JW, LZ and HX contributed to the conception and design of the study; SC, JW and LZ performed the experiments, collected and analyzed data; SC and JW wrote the manuscript; all authors reviewed and approved the final version of the manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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