Open AccessDeregulation of XBP 1 expression contributes to myocardial vascular endothelial growth factor‐A expression and angiogenesis during cardiac hypertrophy in vivo
Author(s) -
Duan Quanlu,
Ni Li,
Wang Peihua,
Chen Chen,
Yang Lei,
Ma Ben,
Gong Wei,
Cai Zhejun,
Zou MingHui,
Wang Dao Wen
Publication year - 2016
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12460
Subject(s) - xbp1 , angiogenesis , vascular endothelial growth factor , medicine , downregulation and upregulation , biology , endocrinology , unfolded protein response , endoplasmic reticulum , heart failure , pressure overload , vascular endothelial growth factor a , muscle hypertrophy , microbiology and biotechnology , cardiac hypertrophy , rna , biochemistry , rna splicing , gene , vegf receptors
Summary Endoplasmic reticulum ( ER ) stress has been reported to be involved in many cardiovascular diseases such as atherosclerosis, diabetes, myocardial ischemia, and hypertension that ultimately result in heart failure. XBP 1 is a key ER stress signal transducer and an important pro‐survival factor of the unfolded protein response ( UPR ) in mammalian cells. The aim of this study was to establish a role for XBP 1 in the deregulation of pro‐angiogenic factor VEGF expression and potential regulatory mechanisms in hypertrophic and failing heart. Western blots showed that myocardial XBP 1s protein was significantly increased in both isoproterenol ( ISO )‐induced and pressure‐overload‐induced hypertrophic and failing heart compared to normal control. Furthermore, XBP 1 silencing exacerbates ISO ‐induced cardiac dysfunction along with a reduction of myocardial capillary density and cardiac expression of pro‐angiogenic factor VEGF ‐A in vivo . Consistently, experiments in cultured cardiomyocytes H9c2 (2‐1) cells showed that UPR ‐induced VEGF ‐A upregulation was determined by XBP 1 expression level. Importantly, VEGF ‐A expression was increased in failing human heart tissue and blood samples and was correlated with the levels of XBP 1. These results suggest that XBP 1 regulates VEGF ‐mediated cardiac angiogenesis, which contributes to the progression of adaptive hypertrophy, and might provide novel targets for prevention and treatment of heart failure.