lncExACT1和DCHS2调节心脏生理和病理生长
Haobo Li1, Lena E Trager1, Xiaojun Liu1
1Corrigan-Minehan Heart Center and Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (H.L., L.E.T., X.L., M.H.H., C.X., J.G., S.T., G.L., A.Y., R.R., M.G.S., S.D., J.M.G.-R., A.R.).
Circulation
|February 4, 2022
概括
一种新的长非编码RNA lncExACT1 和它的下游目标DCHS2 作为心脏生长的主开关,区分有益的生理性缩和有害的病理性缩和心力衰竭.
科学领域:
- 心血管生物学
- 分子心脏病学
- 核糖核酸生物学
背景情况:
- 心脏生长是对生理和病理刺激的反应,结果不同.
- 身体过度增生保护心脏,而病理过度增生可能导致心脏衰竭.
- 长非编码RNAs (lncRNAs) 在生理心脏生长中的作用在很大程度上是未知的.
研究的目的:
- 研究 lncRNAs 在运动诱导的心脏缩和心肌形成中的作用.
- 确定调节生理和病理心脏生长之间的新分子通路.
主要方法:
- 运动或横向大动脉收缩的小鼠心脏的RNA测序.
- 使用腺相关病毒载体和抗意义锁定核酸 GapmeRs 的候选 lncRNAs 的过度表达和抑制.
- 包括DCHS2在内的下游效应器在斑马鱼和小鼠中的功能研究.
主要成果:
- 鉴定了运动调节的心脏 lncRNAs (lncExACTs),其中 lncExACT1 在生理和病理条件下显示相反的调节.
- lncExACT1过度表达导致病理性缩和心力衰竭;抑制促进了生理性缩,并防止了纤维化.
- lncExACT1-DCHS2通路调节微RNA-222,素素和Hippo/Yap1信号传递,控制心脏生长结果.
结论:
- 这种 lncExACT1- DCHS2 途径是心脏缩和心肌形成的新型调节剂.
- 这条路径作为主开关, 确定心脏生长是否有益或有害.
- 针对 lncExACT1-DCHS2 途径为心脏病提供了潜在的治疗策略.
相关概念视频
01:30Cardiomyopathy II: Dilated Cardiomyopathy
51
Dilated cardiomyopathy, or DCM, is a progressive myocardial disorder characterized by ventricular chamber dilation and contractile dysfunction.EtiologyVarious factors can cause DCM, including hypertension and heavy alcohol intake, which contribute to the weakening and enlargement of the heart muscle. Viral infections, such as Coxsackievirus B, adenoviruses, and influenza, can lead to DCM by causing inflammation and damage to heart tissue. Certain chemotherapeutic agents, including daunorubicin,...
51
01:29Cardiomyopathy III: Hypertrophic Cardiomyopathy
79
Hypertrophic cardiomyopathy, or HCM, is an autosomal dominant genetic disorder characterized by asymmetric left ventricular hypertrophy without ventricular dilation. It is more common in men and is typically diagnosed in young, athletic adults.EtiologyHCM is primarily genetic and is caused by mutations in genes encoding sarcomeric proteins. Researchers have identified over 1400 mutations across at least 11 different genes. Among these, the most frequently occurring mutations are found in the...
79