title: REDD1 attenuates cardiac hypertrophy via enhancing autophagy.
abstract: Cardiac hypertrophy is a major risk factor of cardiovascular morbidity and mortality. Autophagy is established to be involved in regulating cardiac hypertrophy. REDD1, a stress-responsive protein, is proved to contribute in autophagy induction. However, the role of REDD1 in cardiac hypertrophy remains unknown. Our study demonstrated that REDD1 knockdown by RNAi exacerbated phenylephrine (PE)-induced cardiac hypertrophy, manifested by increased hypertrophic markers such as ANP and cell surface area. In addition, we discovered that ERK1/2 signaling pathway was involved in the effect of REDD1 on hypertrophy. Moreover, our study showed that REDD1 knockdown impaired autophagy in hypertrophied cardiomyocytes. mTOR, a signaling molecule governing autophagy induction, was activated by the knockdown of REDD1 under PE stress. Importantly, the pro-hypertrophic effect of REDD1 knockdown was significantly reversed by the autophagy enhancer rapamycin. Taken together, we firstly prove that REDD1 is essential for inhibiting cardiac hypertrophy by enhancing autophagy.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China; Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou 510080, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China; Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou 510080, China.
authors.forename: Ruicong
authors.initials: R
authors.lastname: Xue
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China; Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou 510080, China.
authors.forename: Dexi
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China; Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou 510080, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China; Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou 510080, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Respiratory, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Tan
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China; Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou 510080, China.
authors.forename: Yili
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China; Key Laboratory on Assisted Circulation, Ministry of Health, Guangzhou 510080, China. Electronic address: dongxg@mail.sysu.edu.cn.
authors.forename: Yugang
authors.initials: Y
authors.lastname: Dong
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006332:Cardiomegaly / Q000378:metabolism* / Q000473:pathology* / Q000517:prevention & control; D049108:Cell Enlargement / Q000187:drug effects; D002478:Cells, Cultured; D055785:Gene Knockdown Techniques; D020935:MAP Kinase Signaling System; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010656:Phenylephrine / Q000633:toxicity; D051381:Rats; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology; D014157:Transcription Factors
chemical_list: C000632146:Ddit4 protein, rat; D012097:Repressor Proteins; D014157:Transcription Factors; D010656:Phenylephrine; D020123:Sirolimus
keywords: Autophagy; Cardiac hypertrophy; REDD1; mTOR