title: Smad Nuclear Interacting Protein 1 Acts as a Protective Regulator of Pressure Overload-Induced Pathological Cardiac Hypertrophy.
abstract: Smad nuclear interacting protein 1 (SNIP1) plays a critical role in cell proliferation, transformation of embryonic fibroblasts, and immune regulation. However, the role of SNIP1 in cardiac hypertrophy remains unclear.
  
  
  
  Here we examined the role of SNIP1 in pressure overload-induced cardiac hypertrophy and its mechanisms. Our results demonstrated that SNIP1 expression was downregulated in human dilated cardiomyopathic hearts, aortic banding-induced mice hearts, and angiotensin II-treated cardiomyocytes. Accordingly, SNIP1 deficiency significantly exacerbated aortic banding-induced cardiac hypertrophy, fibrosis, and contractile dysfunction, whereas cardiac-specific overexpression of SNIP1 markedly recovered pressure overload-induced cardiac hypertrophy and fibrosis. Besides that, SNIP1 protected neonatal rat cardiomyocytes against angiotensin II-induced hypertrophy in vitro. Moreover, we identified that SNIP1 suppressed nuclear factor-κB signaling during pathological cardiac hypertrophy, and inhibition of nuclear factor-κB signaling by a cardiac-specific conditional inhibitor of κBS32A/S36Atransgene blocked these adverse effects of SNIP1 deficiency on hearts.
  
  
  
  Together, our findings demonstrated that SNIP1 had protective effects in pressure overload-induced pathological cardiac hypertrophy via inhibition of nuclear factor-κB signaling. Thus, SNIP1 may be a novel approach for the treatment of heart failure.
authors.affiliation: Department of Cardiology, Cardiovascular Disease Institute, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Yu-Yan
authors.initials: YY
authors.lastname: Lu
authors.affiliation: Department of Cardiology, Cardiovascular Disease Institute, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Da-Chun
authors.initials: DC
authors.lastname: Xu
authors.affiliation: Department of Cardiology, Cardiovascular Disease Institute, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Yi-Fan
authors.initials: YF
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, Cardiovascular Disease Institute, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Guo-Fu
authors.initials: GF
authors.lastname: Zhu
authors.affiliation: Department of Cardiology, Cardiovascular Disease Institute, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Meng-Yun
authors.initials: MY
authors.lastname: Zhu
authors.affiliation: Department of Cardiology, Cardiovascular Disease Institute, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Wei-Jing
authors.initials: WJ
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Cardiovascular Disease Institute, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Xue-Jing
authors.initials: XJ
authors.lastname: Yu
authors.affiliation: Department of Cardiology, Cardiovascular Disease Institute, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Cardiovascular Disease Institute, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Cardiovascular Disease Institute, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China xuyawei@tongji.edu.cn.
authors.forename: Ya-Wei
authors.initials: YW
authors.lastname: Xu
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D006332:Cardiomegaly / Q000517:prevention & control*; D004195:Disease Models, Animal; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism / Q000502:physiology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032383:Myocytes, Cardiac; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D016601:RNA-Binding Proteins; D015398:Signal Transduction / Q000502:physiology
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D016601:RNA-Binding Proteins; C485848:Snip1 protein, mouse
keywords: Smad nuclear interacting protein 1; cardiac hypertrophy; heart failure; nuclear factor‐κB; signaling pathway