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The Association of Depressed Angiogenic Factors with Reduced Capillary Density in Rhesus Monkey Model of Myocardial Ischemic Infarction
Author(s) -
Zhang Wenjing,
Zhao Xinmei,
Xiao Ying,
Han Pengfei,
Kang James
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.798.6
Subject(s) - myocardial infarction , hypoxia (environmental) , vascular endothelial growth factor , angiogenesis , medicine , endocrinology , basic fibroblast growth factor , hypoxia inducible factors , growth factor , receptor , cardiology , biology , chemistry , vegf receptors , gene , biochemistry , organic chemistry , oxygen
Depressed capillary density is associated with myocardial ischemic infarction, in which hypoxia‐inducible factor 1α (HIF‐1α) is increased. The present study was undertaken to examine changes in the angiogenic factors whose expression is regulated by HIF‐1 and their relation to the depressed capillary density in Rhesus monkey model of myocardial ischemic infarction. The density of capillary vessels was considerably decreased but the concentrations of HIF‐1α and HIF‐1β were significantly increased in the infarct area. However, the levels of mRNA and protein for vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR)‐1 were significantly decreased in the same area of HIF‐1 elevation.Other angiogenic factors whose expression is regulated by HIF‐1, including Tie‐2, angiopoietin (Ang)‐1 and fibroblast growth factor (FGF)‐1, were also significantly depressed, while factors not regulated by HIF‐1, including VEGFR‐2 and Ang‐2, were significantly increased.In addition, the concentration of Cu, which is required for HIF‐1 regulation of the expression of angiogenic factors, was significantly decreased. The data suggest that although HIF‐1 concentration increases in the ischemic infarct area, Cu loss suppresses its transcriptional activity leading to inhibition of the expression of angiogenic factors and the subsequent depression of vascular density. Supported by National Science Foundation of China (81230004).