Open AccessSmad Nuclear Interacting Protein 1 Acts as a Protective Regulator of Pressure Overload‐Induced Pathological Cardiac Hypertrophy
Author(s) -
Lu Yuyan,
Xu Dachun,
Zhao Yifan,
Zhu Guofu,
Zhu Mengyun,
Liu Weijing,
Yu Xuejing,
Chen Wei,
Liu Zheng,
Xu Yawei
Publication year - 2016
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.116.003943
Subject(s) - pressure overload , muscle hypertrophy , medicine , angiotensin ii , heart failure , fibrosis , cardiac fibrosis , smad , endocrinology , cardiac hypertrophy , transforming growth factor , cardiology , blood pressure
Background Smad nuclear interacting protein 1 ( SNIP 1) plays a critical role in cell proliferation, transformation of embryonic fibroblasts, and immune regulation. However, the role of SNIP 1 in cardiac hypertrophy remains unclear. Methods and Results Here we examined the role of SNIP 1 in pressure overload–induced cardiac hypertrophy and its mechanisms. Our results demonstrated that SNIP 1 expression was downregulated in human dilated cardiomyopathic hearts, aortic banding‐induced mice hearts, and angiotensin II –treated cardiomyocytes. Accordingly, SNIP 1 deficiency significantly exacerbated aortic banding–induced cardiac hypertrophy, fibrosis, and contractile dysfunction, whereas cardiac‐specific overexpression of SNIP 1 markedly recovered pressure overload–induced cardiac hypertrophy and fibrosis. Besides that, SNIP 1 protected neonatal rat cardiomyocytes against angiotensin II –induced hypertrophy in vitro. Moreover, we identified that SNIP 1 suppressed nuclear factor‐κB signaling during pathological cardiac hypertrophy, and inhibition of nuclear factor‐κB signaling by a cardiac‐specific conditional inhibitor of κ B S 32A/S36A transgene blocked these adverse effects of SNIP 1 deficiency on hearts. Conclusions Together, our findings demonstrated that SNIP 1 had protective effects in pressure overload–induced pathological cardiac hypertrophy via inhibition of nuclear factor‐κB signaling. Thus, SNIP 1 may be a novel approach for the treatment of heart failure.