Critical role of angiopoietins/Tie-2 in hyperglycemic exacerbation of myocardial infarction and impaired angiogenesis

摘要

Tie-2 is a receptor tyrosine kinase that is expressed in the vascular endothelium; angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) are the two ligands of the Tie-2 receptor (18,44). Ang-1 is an agonist that binds to Tie-2 and mediates Tie-2 autophos-phorylation promoting endothelial cell survival by activation of the protein kinase B/Akt pathway. Ang-2 is an antagonist of the Tie-2 receptor. Systemic elevation of Ang-2 levels has a detrimental effect as evidenced by the embryonic lethal phenotype of transgenic mice with Ang-2 overexpression (18, 28). Recent studies demonstrate that under hyperoxic conditions Ang-2 and its receptor Tie-2 are stimulated, while Ang-1 is inhibited. Increased Ang-2 levels in vivo after exposure to hyperoxia have been implicated in the pathogenesis of oxidant lung injury, cell death, inflammation, vascular leakage, and mortality (2, 3).