Department of Clinical Laboratory, Peking University People's Hospital, Beijing, People's Republic of China
State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
Biosci Rep. 2018 Mar 9;38(2). doi: 10.1042/BSR20171430. Print 2018 Apr 27.
Hypertrophic cardiomyopathy (HCM) is a serious monogenic disease characterized by cardiac hypertrophy, fibrosis, sudden cardiac death, and heart failure. Previously, we identified that was down-regulated in HCM patients. However, the regulatory effects of remain unclear. Thus, we investigated the role of in the regulation of cardiac hypertrophy. The expression of in left ventricular tissues in HCM patients and mice subjected to transverse aortic constriction (TAC) was significantly down-regulated. Knockdown of expression in neonatal rat cardiomyocytes (NRCMs) induced cardiomyocyte enlargement and increased atrial natriuretic polypeptide (ANP) expression. Overexpression of antagonized isoproterenol (ISO)-induced cardiomyocyte enlargement and ANP/brain natriuretic peptide (BNP) up-regulation. More importantly, we found that c-Jun expression was inhibited by in NRCMs. Knockdown of c-Jun expression significantly attenuated cardiac hypertrophy induced by deprivation. Our data indicated that was down-regulated in the hearts of HCM patients and that it inhibited cardiac hypertrophy by targetting c-Jun expression.
肥厚型心肌病（HCM）是一种严重的单基因疾病，其特征为心肌肥厚、纤维化、心源性猝死和心力衰竭。此前，我们发现 在 HCM 患者中表达下调。然而， 对心脏肥大的调节作用仍不清楚。因此，我们研究了 在调节心脏肥大中的作用。HCM 患者和接受主动脉缩窄（TAC）的小鼠左心室组织中 的表达明显下调。在乳鼠心肌细胞（NRCMs）中敲低 的表达会诱导心肌细胞增大并增加心房利钠肽（ANP）的表达。过表达 拮抗异丙肾上腺素（ISO）诱导的心肌细胞增大和 ANP/脑利钠肽（BNP）的上调。更重要的是，我们发现 c-Jun 的表达在 NRCMs 中被 抑制。敲低 c-Jun 的表达显著减轻了 剥夺引起的心脏肥大。我们的数据表明， 在 HCM 患者的心脏中表达下调，通过靶向 c-Jun 表达抑制心脏肥大。
