雌二醇通过PTEN/AKT信号通路促进自噬参与冠状动脉病变过程

Estradiol promotes autophagy through the PTEN/AKT signaling pathway to participate in coronary artery disease

目的:探讨冠心病人群中雌二醇、IL-6水平与冠状动脉病变程度的相关性,通过人脐静脉内皮细胞(human umbilical vein endothelial cell,HUVEC)研究雌二醇是否通过PTEN/AKT信号通路,促进内皮细胞发生自噬,从而减少ox-LDL诱导的IL-6的释放,抑制HUVEC炎症反应。方法:根据相关标准选取新乡医学院第一附属医院心脏中心生物样本库中2017—2018年行冠状动脉造影女性患者84例,年龄≤55岁,根据Gensini评分进行分组,测定各组血浆雌二醇、IL-6的含量并分析二者与冠状动脉造影Gensini评分的相关性。为进一步阐明雌二醇与冠脉病变程度的相关性,通过雌二醇干预HUVEC细胞,运用MTT法检测细胞活性;Western Blot法检测PTEN,p-AKT,LC3A/B和Beclin-1的蛋白表达。结果:冠状动脉病变各组血浆中雌二醇含量随着Gensini评分升高而呈不同程度降低,其中GS=1~19组、GS=19~48和GS> 48呈统计学下降(P <0. 05或P <0. 01)。IL-6含量则随着Gensini评分升高而升高,其中GS> 48组在统计学上升高(P <0. 01)。ox-LDL可促进HUVEC释放炎症因子IL-6,雌二醇能抑制ox-LDL诱导的IL-6释放;雌二醇通过上调PTEN蛋白,使p-AKT激活减少,从而促进细胞发生自噬,进而抑制IL-6的释放。结论:雌二醇与冠脉病变程度呈负相关,IL-6含量与冠脉病变程度呈正相关,其机制与雌二醇通过PTEN/AKT信号通路促进内皮细胞发生自噬,从而减少ox-LDL诱导的IL-6的释放,进而影响冠状动脉病变进程。

Objective:To investigate the correlation of estradiol,IL-6 levels and coronary artery lesions in patients with coronary heart disease,human umbilical vein endothelial cells(HUVEC)were used to investigate whether estradiol promotes autophagy in endothelial cells through PTEN/AKT signaling pathway,thereby reducing ox-LDL-induced IL-6 release and inhibiting HUVEC inflammatory response.Methods:According to the relevant criteria,84 female patients(≤55 years old)were selected from the those who underwent coronary angiography in heart sample library of the First Affiliated Hospital of Xinxiang Medical College in 2017-2018.To further elucidate the correlation between estradiol and the severity of coronary artery disease,cell viability was detected by MTTassay after interleukin intervention in HUVEC cells.The protein expressions of PTEN,p-AKT,LC3 A/B and Beclin-1 were detected by Western Blot.Results:The estradiol was decreased with the increase of Gensini score,and GS=1~19 group,GS=19~48 and GS>48 showed a significant decrease(P<0.05,P<0.01).The IL-6 level increased with the increase of Gensini score,and the GS>48 group increased significantly(P<0.01).Further studies showed that ox-LDL promoted the release of inflammatory factor IL-6 from HUVEC,and estradiol inhibited ox-LDL-induced IL-6 release.Further studies showed that estradiol reduced p-AKT activation by up-regulating PTEN protein,thereby promoting autophagy and inhibiting the release of IL-6.Conclusion:This study showed that estradiol was negatively correlated with the degree of coronary artery disease,but IL-6 content was positively correlated with the degree.Regarding the mechanism,estradiol can promote autophagy in HUVEC through PTEN/AKT signaling pathway,thereby reduce ox-LDL-induced IL-6 release,which in turn affect the progression of coronary artery disease.