长链非编码RNALINC00184调控老年高血压血管内皮细胞的增殖与迁移

Regulation of proliferation and migration of vascular endothelial cells in elderly hypertension patients by long non-coding RNA LINC00184

中文关键词: 老年  高血压  长链非编码RNA  血管内皮细胞  LINC00184

英文关键词: elderly  hypertension  long non-coding RNA  endothelial cell  LINC00184

中文摘要:

      目的 高血压是老年人动脉粥样硬化发生和发展的重要致病因素.血管内皮细胞的损伤和衰老加速动脉粥样硬化的发生和发展.作为基因转录和翻译的重要调控元件,长链非编码RNA(lncRNA)已经被证实在多种生物学过程中发挥重要作用,但其在高血压引起动脉粥样硬化以及血管内皮损伤中的作用和分子机制远未了解清楚.方法 回顾性收集上海交通大学医学院附属仁济医院2019年5月-2020年12月老年医学科门诊具备完整病史资料的老年患者(≥60岁)共51例,根据血压及颈动脉内膜中层厚度(CIMT)分为3组:高血压伴动脉粥样硬化组、高血压不伴动脉粥样硬化组和无高血压的动脉粥样硬化组.通过荧光定量PCR检测高血压以及高血压伴动脉粥样硬化患者血液中的lncRNA的表达.在人血管内皮细胞中,通过转染siRNA的方式敲减LINC00184,通过免疫荧光等形态学方法检测内皮细胞的增殖与迁移是否受到影响.利用荧光素酶报告基因、免疫印迹等方法,明确LINC00184参与调控血管内皮细胞的作用机制.结果 3组间的CIMT、收缩压和舒张压有显著差异(P＜0.05);LINC00184在老年高血压患者的血浆中高表达;LINC00184在人血管内皮细胞中高表达,且主要分布于细胞质中;敲减LINC00184导致血管内皮细胞增殖和迁移能力增强;LINC00184通过影响miR-17调控PTEN的表达参与血管内皮细胞的功能.结论 老年高血压相关LINC0184参与调控血管内皮细胞的增殖和迁移,为进一步探究高血压导致的靶器官损伤的分子机制提供理论依据.

英文摘要:

      Objective Hypertension is an important pathogenic factor in the occurrence and development of atherosclero-sis in the elderly.The damage and aging of vascular endothelial cells accelerate the occurrence and development of atherosclero-sis.Long chain non-coding RNA(lncRNA)has been proved to play an important role in a variety of biological processes,but its role and molecular mechanism in hypertension-induced atherosclerosis and vascular endothelial damage are far from clear.Methods 51 elderly patients(≥60 years old)with complete medical history data from Department of Geriatrics,Renji Hospital from May 2019 to December 2020 were retrospectively collected.They were divided into three groups based on carotid intima-media thickness(CIMT)and blood pressure:hypertension with atherosclerosis group,hypertension without atherosclerosis group and atherosclerosis without hypertension group.The expression level of lncRNA in patients'blood was detected by fluorescence quantitative PCR.In human vascular endothelial cells,LINC00184 was knocked down by transfection of siRNA,and then the effects on the proliferation and migration of endothelial cells were assessed by morphological methods such as immunofluores-cence.The mechanism of LINC00184 involved in the regulation of vascular endothelial cells was determined by luciferase reporter gene assays and immunoblotting.Results There were significant differences in CIMT,systolic blood pressure and diastolic blood pressure among the three groups(P＜0.05).LINC00184 was highly expressed in plasma of elderly patients with hypertension.LINC00184 was highly expressed in human vascular endothelial cells and mainly distributed in the cytoplasm.Knockdown of LINC00184 could enhance the proliferation and migration of vascular endothelial cells.LINC00184 was involved in the function of vascular endothelial cells by influencing miR-17 to regulate the expression of PTEN.Conclusion LINC00184 is involved in the regulation of the proliferation and migration of vascular endothelial cells in elderly hypertension patients,which provides a theo-retical basis for further exploring the molecular mechanism of target organ damage caused by hypertension.