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自噬相关基因5和细胞周期蛋白E在冠心病中的表达及其临床意义。

Expression of autophagy related gene 5 and cyclin E in coronary heart disease and its clinical significance.

作者信息

Kang Jianmei, Ding Zhouli, Luo Yingquan, Yang Yu

机构信息

Department of Geriatrics, Second Xiangya Hospital, Central South University, Changsha 410011, China.

出版信息

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2020 Jan 28;45(1):17-23. doi: 10.11817/j.issn.1672-7347.2020.180610.

Abstract

OBJECTIVES

To explore the expression of autophagy related genes 5 (ATG5) and cyclin E in coronary heart disease (CHD) and its clinical significance.

METHODS

From April 2018 to August 2018, 80 patients diagnosed with CHD in the Second Xiangya Hospital, Central South University were selected as an observation group, and another 80 healthy subjects were selected as a control group. The expression of ATG5 and cyclin E mRNA in nucleate cells and the plasma protein in the 2 groups were detected and analyzed. The model of macrophage-derived foam cells induced by oxidized low density lipoprotein (ox-LDL) was used to simulate atherosclerosis. The proliferation of macrophage- derived foam cells and the protein levels of ATG5 and cyclin E induced by ox-LDL at different concentrations were examined.

RESULTS

Compared with the control group, the levels of ATG5 mRNA and protein in the blood in the observation group were decreased, and the cyclin E mRNA and protein levels were increased, there were statistically difference (both <0.05). Receiver operating characteristic (ROC) curve showed that the area under curve (AUC) of ATG5 mRNA, cyclin E mRNA, ATG5 protein and cyclin E protein were 0.739, 0.780, 0.671 and 0.807, respectively. Pearson analysis showed that the ATG5 mRNA was negatively correlated with the cyclin E mRNA (=-0.734, <0.05),while the plasma ATG5 protein was negatively correlated with the plasma cyclin E protein (=-0.746, <0.05). Macrophage-derived foam cell model induced by ox-LDL showed that the proliferation of foam cells and the expression levels of cyclin E protein were increased in a concentration and time-dependent manner, and the expression levels of ATG5 protein were decreased in a concentration-dependent manner.

CONCLUSIONS

The levels of ATG5 mRNA and protein are lowly expressed while the levels of cyclin E mRNA and protein are highly expressed in the patients with CHD.The ATG5 protein levels are lowly expressed in ox-LDL-treated macrophage-derived foam cells while the cyclin E protein levels are highly expressed in ox-LDL-treated macrophage-derived foam cells. Based on these observations, we conclude that ATG5 inhibits the degradation of the cyclin E and promotes the proliferation of macrophages, involving in the occurrence and development of CHD.

摘要

目的

探讨自噬相关基因5(ATG5)和细胞周期蛋白E在冠心病(CHD)中的表达及其临床意义。

方法

选取2018年4月至2018年8月在中南大学湘雅二医院确诊为冠心病的80例患者作为观察组,另选取80例健康受试者作为对照组。检测并分析两组有核细胞中ATG5和细胞周期蛋白E mRNA的表达及血浆蛋白水平。采用氧化型低密度脂蛋白(ox-LDL)诱导巨噬细胞源性泡沫细胞模型模拟动脉粥样硬化。检测不同浓度ox-LDL诱导的巨噬细胞源性泡沫细胞的增殖情况以及ATG5和细胞周期蛋白E的蛋白水平。

结果

与对照组相比,观察组血液中ATG5 mRNA和蛋白水平降低,细胞周期蛋白E mRNA和蛋白水平升高,差异均有统计学意义(均P<0.05)。受试者工作特征(ROC)曲线显示,ATG5 mRNA、细胞周期蛋白E mRNA、ATG5蛋白和细胞周期蛋白E蛋白的曲线下面积(AUC)分别为0.739、0.780、0.671和0.807。Pearson分析显示,ATG5 mRNA与细胞周期蛋白E mRNA呈负相关(r=-0.734,P<0.05),而血浆ATG5蛋白与血浆细胞周期蛋白E蛋白呈负相关(r=-0.746,P<0.05)。ox-LDL诱导的巨噬细胞源性泡沫细胞模型显示,泡沫细胞的增殖和细胞周期蛋白E蛋白的表达水平呈浓度和时间依赖性增加,而ATG5蛋白的表达水平呈浓度依赖性降低。

结论

冠心病患者中ATG5 mRNA和蛋白水平低表达,而细胞周期蛋白E mRNA和蛋白水平高表达。ox-LDL处理的巨噬细胞源性泡沫细胞中ATG5蛋白水平低表达,而细胞周期蛋白E蛋白水平高表达。基于这些观察结果,我们得出结论,ATG5抑制细胞周期蛋白E的降解并促进巨噬细胞增殖,参与冠心病的发生发展。

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