Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
Aging (Albany NY). 2020 Feb 21;12(4):3126-3139. doi: 10.18632/aging.102668.
Hearts often undergo abnormal remodelling and hypertrophic growth in response to pathological stress. Long non-coding RNAs (LncRNAs) can change cardiac function and participate in regulation of cardiac hypertrophy. The present study aims to identify the role of AK045171 in cardiac hypertrophy and the underlying mechanism in hypertrophic cascades. Mice with cardiac hypertrophy were established through transverse aortic constriction (TAC). Cardiac hypertrophy in cardiomyocytes was induced by angiotensin II (angII). The expression of AK045171 and its target gene SP1 was examined in cardiomyocytes transfected with miRNA. The AK045171 expression level was downregulated in mice after TAC surgery. Overexpression of AK045171 attenuated cardiac hypertrophy both in vitro and in vivo. The mechanism study indicated that AK045171 binds with SP1, which promotes transcription activation of MEG3. It is suggested that overexpression of AK045171 might have clinical potential to suppress cardiac hypertrophy and heart failure.
心脏常常会发生异常重塑和肥厚生长，以应对病理性压力。长链非编码 RNA（lncRNA）可改变心脏功能，并参与心脏肥厚的调控。本研究旨在鉴定 AK045171 在心脏肥厚及其在肥厚级联反应中的潜在机制中的作用。通过横主动脉缩窄（TAC）建立心脏肥厚的小鼠模型。用血管紧张素 II（angII）诱导心肌细胞的心肌肥厚。用 miRNA 转染的心肌细胞检测 AK045171 及其靶基因 SP1 的表达。TAC 手术后，小鼠的 AK045171 表达水平下调。AK045171 的过表达在体外和体内均减轻了心肌肥厚。机制研究表明，AK045171 与 SP1 结合，促进 MEG3 的转录激活。提示 AK045171 的过表达可能具有抑制心脏肥厚和心力衰竭的临床潜力。
