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High glucose blunts angiopoietin‐1 (Ang‐1)‐induced angiogenesis in myocardial endothelial cells via impairment of Akt and eNOS phosphorylation.
Author(s) -
Tuo Qinhui,
Yu Heidi,
Chen JianXiong
Publication year - 2007
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.21.5.a130-b
Subject(s) - angiogenesis , enos , protein kinase b , medicine , endocrinology , angiopoietin , phosphorylation , downregulation and upregulation , signal transduction , chemistry , microbiology and biotechnology , vascular endothelial growth factor , biology , nitric oxide , nitric oxide synthase , biochemistry , vegf receptors , gene
Hyperglycemia is a major risk factor for diabetic complications and has been contributed to the impairment of angiogenesis. Ang‐1/Akt/eNOS pathway has an important role in regulating angiogenesis, but little is known about the role of Ang‐1 on myocardial angiogenesis under hyperglycemic conditions. We investigate the role of Ang‐1 on high glucose (HG)‐induced impairment of angiogenic signaling pathways and angiogenesis. Our data demonstrate that exposure of mouse heart microvascular endothelial cells (MHMECs) to HG (30 mM/L) for 4 days increases angiopoietin‐2 and decreases Tie‐2 expression. This is accompanied by a dramatic suppression of Ang‐1‐induced Akt and eNOS phosphorylation under HG conditions. Furthermore, Ang‐1‐stimulated MHMECs migration, tubule formation, and mouse aortic ring sprouts were blunted under HG compared to low glucose (LG). Overexpression of Ang‐1 and Akt by transfected MHMECs with Ad‐Ang‐1 or Ad AktMyr significantly attenuated HG‐induced impairment of angiogenic response. We concluded that HG impaired angiogenesis in MHMECs via inhibition of Ang‐1/Akt/eNOS pathway. Our data implicated that upregulation of Ang‐1/Akt/eNOS signaling pathway in myocardium should be considered as a novel therapeutic strategy in protecting the diabetic cardiovascular complications. This work is supported by grants from AHA 0565196B and DK074995.