Experimental Study on Alleviating Atherosclerosis through Intervention of Mitochondrial Calcium Transport and Calcium-Induced Membrane Permeability Transition

Abstract

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.