Xue Yu-Zeng, Li Zhi-Juan, Liu Wei-Tao, Shan Jin-Jiao, Wang Lei, Su Qian
Cardiology Department, Liaocheng People's Hospital, Liaocheng 252000, Shandong Province, PR.China.
Cardiovascular Department, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, Henan Province, PR.China.
Aging (Albany NY). 2019 Jul 25;11(14):5192-5205. doi: 10.18632/aging.102113.
Recently, the effect of long non-coding RNAs (lncRNAs) in hypertension (HTN) has been identified. This study aims to explore the expression of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in HTN and its role in vascular lesion and remodeling of HTN rats.
LncRNA MALAT1 expression was up-regulated in HTN patients, and lncRNA MALAT1 could be an effective index of HTN diagnosis. Down-regulated MALAT1 and inhibited Notch-1 could reduce relative factor expression, including inflammation-related factors, endothelial function-related factors and oxidative stress-related factors, and inhibit apoptosis of aortic endothelial cells of HTN rats.
LncRNA MALAT1 expression in HTN patients and healthy controls was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Angiotensin II (Ang II)-induced HTN rat models were injected with MALAT1-siRNA, empty lentivirus vector, Notch pathway inhibitor (DAPT) and dimethyl sulphoxide (DMSO) via caudal vein. After three-week treatment, changes of blood pressure, inflammatory factor levels, endothelial function-related factors, oxidative stress indices and apoptosis of vascular endothelial cells were determined by a series of assays.
This study revealed that down-regulated lncRNA MALAT1 could alleviate the vascular lesion and remodeling of HTN rats, the mechanism may be related to the inhibited activation of Notch signaling pathway.
近年来,已明确长链非编码RNA(lncRNA)在高血压(HTN)中的作用。本研究旨在探讨lncRNA转移相关肺腺癌转录本1(MALAT1)在HTN中的表达及其在HTN大鼠血管病变和重塑中的作用。
HTN患者中lncRNA MALAT1表达上调,lncRNA MALAT1可能是HTN诊断的有效指标。下调MALAT1并抑制Notch-1可降低包括炎症相关因子、内皮功能相关因子和氧化应激相关因子在内的相关因子表达,并抑制HTN大鼠主动脉内皮细胞凋亡。
采用逆转录定量聚合酶链反应(RT-qPCR)检测HTN患者和健康对照者中lncRNA MALAT1的表达。通过尾静脉向血管紧张素II(Ang II)诱导的HTN大鼠模型注射MALAT1-siRNA、空慢病毒载体、Notch通路抑制剂(DAPT)和二甲基亚砜(DMSO)。治疗三周后,通过一系列检测确定血压、炎症因子水平、内皮功能相关因子、氧化应激指标和血管内皮细胞凋亡的变化。
本研究表明,下调lncRNA MALAT1可减轻HTN大鼠的血管病变和重塑,其机制可能与抑制Notch信号通路激活有关。