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.
| Original language | English (US) |
|---|---|
| Article number | 338 |
| Journal | Basic research in cardiology |
| Volume | 108 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jan 1 2013 |
Bibliographical note
Funding Information:The animal protocol was approved by the Animal Care and Use Committee of the Renmin Hospital of Wuhan University, China. All surgeries and subsequent analyses were performed in a blinded fashion. Full-length human Vinexin-β cDNA was cloned downstream of the cardiac myosin heavy chain (α-MHC) promoter. Transgenic mice were then produced by microinjection of the α-MHC-Vinexin-β construct into fertilised mouse embryos (C57BL/6 background). Four independent transgenic lines were established. Transgenic mice were identified by PCR analysis of tail genomic DNA. Primers were designed as follows: 5′-ATCTCCCCCATAAGAGTTTGAGTC-3′ and 5′-GGGTGGGTCTTCCAAGGTCCAGTCC-3′. The expected size for the amplification product was 694 bp. The Vinexin-β knockout mouse model was generously provided by the RIKEN Bio Resource Center (BRC) through the National Bio Resource Project of the MEXT, Japan.
Funding Information:
The Vinexin-β knockout mouse model was provided by the RIKEN BRC through the National BioResource Project of the MEXT, Japan. This study was supported by the National Natural Science Foundation of China (Grant Nos. 81170086, 81200071, 3087451 and 30801351), National Science and Technology Support Project (No. 2011BAI15B02 and No. 2012BAI39B05), and the National Basic Research Program of China (Grant No. 2011CB503902) and the Fundamental Research Funds for the Central Universities of China (302274021).
Keywords
- AKT
- Cardiac remodelling
- Hypertrophy
- Vinexin-β
