Smad nuclear interacting protein 1 acts as a protective regulator of pressure overload-induced pathological cardiac hypertrophy

Background-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. methods and results-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/s36a transgene blocked these adverse effects of snip1 deficiency on hearts. conclusions-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. © 2016 the authors.