title: Cellular FLICE-like inhibitory protein protects against cardiac hypertrophy by blocking ASK1/p38 signaling in mice.
abstract: Cellular FLICE-like inhibitory protein (Flip) is a negative regulator of nuclear factor κB signaling which has been shown previously to complicate with cardiac hypertrophy. In the present study, we tested the hypothesis that the knockout of Flip would increase cardiac hypertrophy in vivo and in vitro. The effects of Flip knockout on cardiac hypertrophy were investigated using in vitro and in vivo models. Flip was downregulated in transverse aortic constriction (TAC)-induced animal hearts and cardiomyocytes that had been treated with angiotensin II or phenylephrine for 1 h. An in vivo, heart hypertrophy model, was performed by TAC in Flip knockdown and sham mice. The extent of hypertrophy of heart was quantitated by echocardiography, and further confirmed by pathological and molecular examination of heart tissue samples. Conditional knockout of Flip in the murine heart increases the hypertrophic response induced by TAC, whereas cardiac function was preserved with reduced Flip levels in response to hypertrophic stimuli. Western blot experiments further showed Flip knockout activated markedly ASK1/P38 signaling cascades in vivo and in vitro. In conclusion, Flip preserves cardiac functions and inhibits cardiac hypertrophy partially by blocking ASK1/P38 signaling.
authors.affiliation: Department of Oncology and nursing, Shanghai Pulmonary Hospital of Tongji University, 507 Zhengmin Rd, Yangpu, Shanghai, 200433, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.forename: Lianpin
authors.initials: L
authors.lastname: Wu
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.forename: Yumei
authors.initials: Y
authors.lastname: Li
authors.forename: Lili
authors.initials: L
authors.lastname: Hou
mesh_terms: D000818:Animals; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000235:genetics / Q000378:metabolism*; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D048848:MAP Kinase Kinase Kinase 5 / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D051379:Mice; D018345:Mice, Knockout; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D048051:p38 Mitogen-Activated Protein Kinases; D048848:MAP Kinase Kinase Kinase 5; C482859:Map3k5 protein, mouse
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