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Disruption of angiopoietin‐1/Tie‐2 signaling contributes to the impairment of myocardial vasculature maturation and angiogenesis in db/db mice
Author(s) -
chen Jianxiong,
Stinnet Amanda,
Zeng Heng
Publication year - 2008
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.22.1_supplement.925.2
Subject(s) - angiogenesis , angiopoietin , angiopoietin receptor , medicine , endocrinology , neovascularization , in vivo , biology , vascular endothelial growth factor , microbiology and biotechnology , vegf receptors
We hypothesized that disruption of angiopoietin‐1/Tie‐2 signaling in diabetes would result in impairment of smooth muscle recruitment and vasculature maturation, contributing to impaired myocardial angiogenesis. Our data revealed that myocardial Tie‐2 expression was significantly attenuated whereas angiopoietin‐2 (Ang‐2) was sustained expression in the db/db mice subjected to myocardial ischemia. Interestingly, angiopoietin‐1(Ang‐1)‐induced smooth muscle cells recruitment and the number of smooth muscle cells coverage per vessel area of the infarct vasculature were significantly reduced in db/db mice. This was accompanied by a markedly impairment of ischemia‐induced myocardial capillary and arteriole densities. Systemic administration of adenovirus Ang‐1 rescued the impaired myocardial angiogenesis and smooth muscle cells recruitments in db/db mice. Our data showed that scar formation was significantly reduced in Ad‐Ang‐1 treated db/db mice compared with Ad‐GFP db/db mice. Additionally, hyperglycemia significantly impaired Ang‐1‐induced angiogenic signaling, along with remarkably inhibition of Ang‐1‐induced angiogenic responses both in vitro and ex vivo. Overexpression of Ang‐1 significantly improved the impaired angiogenic responses under hyperglycemic conditions. Our findings underscore the important role of angiopoietin‐1/Tie‐2 signaling in diabetes‐induced impairment of angiogenesis.