Induction of angiopoietin and Tie receptor mRNA expression after cerebral ischemia-reperfusion

The angiopoietin/Tie receptor system may contribute to angiogenesis and vas cular remodeling by mediating interactions of endothelial cells with smooth muscle cells and pericytes. The temporal expression of angiopoietin-1 (Ang po-1), angiopoietin-2 (Angpo-2), Tie-1, and Tie-2 mRNA was studied in a foc al cerebral ischemia model in rats. The cDNA fragments obtained from revers e transcription polymerase chain reaction amplification were cloned and use d as a probe to detect individual genes. Northern blot analysis showed a de layed increase of a 4.4-kb Angpo-1 transcript for up to 2 weeks after ische mia, eightfold higher than the values of the sham-operated controls. A biph asic expression of a 2.4-kb Angpo-2 transcript was noted, peaking at 24 hou rs (6.4-fold) and 2 weeks (4.6- fold) after ischemia, The expression of Tie -2 mRNA (4.3 kb), a receptor for Angpo-1, and Tie-1 mRNA (4.3 lib) also inc reased starting 24 hours after reperfusion and remained elevated for up to 2 weeks after ischemia. The temporal profiles of the expression of these ge nes were different from those of other angiogenic genes such as basic fibro bast growth factor/fibroblast growth factor receptor and vascular endotheli al growth factor/vascular endothelial growth factor receptor and proteolyti c enzymes (tissue-type plasminogen activator and urokinase plasminogen acti vator) and their inhibitors (plasminogen activator inhibitor-1). The expres sion patterns of these genes could be related to progressive tissue liquefa ction and neovascularization after ischemia in this stroke model. Different ial expression of these angiogenesis genes suggests the involvement of comp lex regulatory mechanisms that remain to be characterized.