title: Vinexin-β protects against cardiac hypertrophy by blocking the Akt-dependent signalling pathway.
abstract: Cardiac hypertrophy is the heart's response to hypertrophic stimuli and is associated with increased mortality. Vinexin-β is a vinculin-binding protein that belongs to a family of adaptor proteins and mediates signal transduction and actin cytoskeleton organisation. A previous study has shown that Vinexin-β is ubiquitously expressed and that it is highly expressed in the heart. However, a critical role for Vinexin-β in cardiac hypertrophy has not been investigated. Therefore, to examine the role of Vinexin-β in pathological cardiac hypertrophy, we used Vinexin-β knockout mice and transgenic mice that overexpress human Vinexin-β in the heart. Cardiac hypertrophy was induced by aortic banding (AB). The extent of cardiac hypertrophy was quantitated by echocardiography and pathological and molecular analyses of heart samples. Our results demonstrated that Vinexin-β overexpression in the heart markedly attenuated cardiac hypertrophy, fibrosis, and cardiac dysfunction, whereas loss of Vinexin-β exaggerated the pathological cardiac remodelling and fibrosis response to pressure overload. Further analysis of the in vitro and in vivo signalling events indicated that beneficial Vinexin-β effects were associated with AKT signalling abrogation. Our findings demonstrate for the first time that Vinexin-β is a novel mediator that protects against cardiac hypertrophy by blocking the AKT signalling pathway.
authors: College of Life Sciences, Wuhan University, Wuhan 430072, People's Republic of China.
authors: Ke
authors: K
authors: Chen
authors: Lu
authors: L
authors: Gao
authors: Yu
authors: Y
authors: Liu
authors: Yan
authors: Y
authors: Zhang
authors: Ding-Sheng
authors: DS
authors: Jiang
authors: Xiang
authors: X
authors: Wei
authors: Xue Hai
authors: XH
authors: Zhu
authors: Rui
authors: R
authors: Zhang
authors: Yingjie
authors: Y
authors: Chen
authors: Qinglin
authors: Q
authors: Yang
authors: Noriyuki
authors: N
authors: Kioka
authors: Xiao-Dong
authors: XD
authors: Zhang
authors: Hongliang
authors: H
authors: Li
mesh_terms: D000818:Animals; D015153:Blotting, Western; D006332:Cardiomegaly / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D017931:DNA Primers / Q000737:chemistry; D004452:Echocardiography; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009124:Muscle Proteins / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D048868:Adaptor Proteins, Signal Transducing
chemical_list: D017931:DNA Primers; D009124:Muscle Proteins; D051057:Proto-Oncogene Proteins c-akt; C117452:Sorbs3 protein, mouse; D048868:Adaptor Proteins, Signal Transducing