Carboxyl‐Terminal Modulator Protein Ameliorates Pathological Cardiac Hypertrophy by Suppressing the Protein Kinase B Signaling Pathway. Issue 13 (3rd July 2018)

• Record Type: Journal Article
• Authors: Liu, Xiaoxiong; Yang, Qin; Zhu, Li‐Hua; Liu, Jia; Deng, Ke‐Qiong; Zhu, Xue‐Yong; Liu, Ye; Gong, Jun; Zhang, Peng; Li, Shuyan; Xia, Hao; She, Zhi‐Gang
• Is Part Of: Journal of the American Heart Association. Volume 7:Issue 13(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-07-03
• Subjects: angiotensin II -- aortic banding -- carboxyl‐terminal modulator protein -- pathological cardiac hypertrophy -- signal transduction; Heart -- Diseases -- Periodicals; Cardiovascular system -- Diseases -- Periodicals; Cerebrovascular disease -- Periodicals; Cardiology -- Periodicals; 616.1
• DOI: 10.1161/JAHA.118.008654
• Languages: English
• ISSNs: 2047-9980

Abstract

Abstract : Background: Carboxyl‐terminal modulator protein (CTMP) has been implicated in cancer, brain injury, and obesity. However, the role of CTMP in pathological cardiac hypertrophy has not been identified. Methods and Results: In this study, decreased expression of CTMP was observed in both human failing hearts and murine hypertrophied hearts. To further explore the potential involvement of CTMP in pathological cardiac hypertrophy, cardiac‐specific CTMP knockout and overexpression mice were generated. In vivo experiments revealed that CTMP deficiency exacerbated the cardiac hypertrophy, fibrosis, and function induced by pressure overload, whereas CTMP overexpression alleviated the response to hypertrophic stimuli. Consistent with the in vivo results, adenovirus‐mediated gain‐of‐function or loss‐of‐function experiments showed that CTMP also exerted a protective effect against hypertrophic responses to angiotensin II in vitro. Mechanistically, CTMP ameliorated pathological cardiac hypertrophy through the blockade of the protein kinase B signaling pathway. Moreover, inhibition of protein kinase B activation with LY294002 rescued the deteriorated effect in aortic banding–treated cardiac‐specific CTMP knockout mice. Conclusions: Taken together, these findings imply, for the first time, that increasing the cardiac expression of CTMP may be a novel therapeutic strategy for pathological cardiac hypertrophy.