Department of Vasculocardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province P.B.C, China.
Institution of Cardiovascular Disease, Hubei Key Laboratory of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province P.B.C, China.
Biomed Pharmacother. 2017 Jul;91:1178-1183. doi: 10.1016/j.biopha.2017.04.041. Epub 2017 May 18.
Hypertensive heart disease (HHD) is one of the most important causes of disease-related deaths worldwide and brings great painful for patients. In recent years, increasingly evidences support the role of miRNAs in various physiology processes and human diseases. In the present study, we investigated whether ADRA1A regulated by miR-19b and miR-16 was involved in the pathogenic mechanism of HHD.
HHD mice models were established with injection of Deoxycorticosterone acetate (Doca). Real-time PCR was used to detect miRNAs and ADRA1A expression. Western blot was used to detect ADRA1A expression. Cell apoptosis was determined by assaying caspase3/7 activation.
ADRA1A was the target gene of miR-19b and miR-16, the expression of miR-19b, miR-16 and ADRA1A were significantly increased in Doca-induced HHD cells. MiRNAs (miR-19b, miR-16) inhibitor significantly increased the expression of ADRA1A but decreased relative activity of caspase 3/7. MiRNA antagomir significantly increased the expression of ADRA1A and heart rate (HR), but significantly decreased systolic blood pressure (SBP), artery diastolic blood pressure (ADBP), fibrosis of ventriculus sinister and cell apoptosis of myocardial tissue that induced by Doca. However, the cooperation of miR-19b and miR-16 showed the better effect than either miR-19b or miR-16.
ADRA1A mediated by miR-19b and miR-16 played an important role in HHD, which functioned as a target gene for HHD therapy.
高血压性心脏病（HHD）是全球最重要的疾病相关死亡原因之一，给患者带来了极大的痛苦。近年来，越来越多的证据支持 miRNA 在各种生理过程和人类疾病中的作用。在本研究中，我们研究了 ADRA1A 是否受 miR-19b 和 miR-16 调节，参与 HHD 的发病机制。
通过注射脱氧皮质酮（Doca）建立 HHD 小鼠模型。实时 PCR 用于检测 miRNA 和 ADRA1A 的表达。Western blot 用于检测 ADRA1A 的表达。通过测定 caspase3/7 激活来检测细胞凋亡。
ADRA1A 是 miR-19b 和 miR-16 的靶基因，miR-19b、miR-16 和 ADRA1A 的表达在 Doca 诱导的 HHD 细胞中显著增加。miRNAs（miR-19b、miR-16）抑制剂显著增加 ADRA1A 的表达，但降低 caspase 3/7 的相对活性。miRNA 拮抗剂显著增加 ADRA1A 和心率（HR）的表达，但显著降低收缩压（SBP）、动脉舒张压（ADBP）、左心室纤维化和 Doca 诱导的心肌组织细胞凋亡。然而，miR-19b 和 miR-16 的协同作用比单独的 miR-19b 或 miR-16 效果更好。
受 miR-19b 和 miR-16 调节的 ADRA1A 在 HHD 中发挥重要作用，可作为 HHD 治疗的靶基因。
