Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
Department of Cardiology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
J Investig Med. 2021 Aug;69(6):1156-1160. doi: 10.1136/jim-2020-001765. Epub 2021 Apr 27.
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 Ca in the atherosclerosis group is significantly higher than control group and mitochondrial targeting agent group. But the mean fluorescence intensity of Ca-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.
探讨线粒体钙转运和钙诱导的膜通透性转换在缓解动脉粥样硬化中的作用。
实验小鼠分为三组：对照组（正常饮食的 C57BL/6 小鼠）、动脉粥样硬化组（高脂饮食的载脂蛋白 E 缺陷（ApoE-/-）小鼠）和线粒体靶向剂组（高脂饮食的 ApoE-/-小鼠）。
与对照组和线粒体靶向剂组相比，动脉粥样硬化组 Ca 的平均荧光强度显著升高，但 Ca-ATPase 的平均荧光强度低于其他组。动脉粥样硬化组的巨噬细胞募集（F4/80 阳性面积）和肿瘤坏死因子-α、白细胞介素-6、pyrin 结构域包含蛋白 3、细胞间黏附分子-1、p38 丝裂原活化蛋白激酶和 Jun 激酶 1/2 磷酸化表达均高于其他组。线粒体靶向剂治疗可降低动脉粥样硬化小鼠细胞色素 C 升高和半胱天冬酶-3 切割的水平（p<0.05）。线粒体靶向剂干扰线粒体钙转运和钙诱导的膜通透性转换，抑制 MAPK/JNK 通路激活，抑制泡沫细胞形成，缓解动脉粥样硬化进程。
