Expression of angiopoietin-1, angiopoietin-2, and tie receptors after middle cerebral artery occlusion in the rat.
Vascular endothelial growth factor (VEGF), a key regulator of vasculogenesis and embryonic angiogenesis, was recently found to be up-regulated in an animal model of stroke. Unlike VEGF, angiopoietin (Ang)-1 and -2, their receptor tie-2, and the associated receptor tie-1 exert their functions at later stages of vascular development, i.e., during vascular remodeling and maturation. To assess the role of the angiopoietin/tie family in ischemia-triggered angiogenesis we analyzed their temporal and spatial expression pattern after middle cerebral artery occlusion (MCAO) using in situ hybridization and immunohistochemistry. Ang-1 mRNA was constitutively expressed in a subset of glial and neuronal cells with no apparent change in expression after MCAO. Ang-2 mRNA was up-regulated 6 hours after MCAO and was mainly observed in endothelial cell (EC) cord tips in the peri-infarct and infarct area. Up-regulation of both Ang-2 and VEGF coincided with EC proliferation. Interestingly, EC proliferation was preceded by a transient period of EC apoptosis, correlating with a change in VEGF/Ang-2 balance. Our observation of specific stages of vascular regression and growth after MCAO are in agreement with recent findings suggesting a dual role of Ang-2 in blood vessel formation, depending on the availability of VEGF.
Beck
H
H
Abteilung Neuropathologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany. heikebeck@gmx.de
Acker
T
T
Wiessner
C
C
Allegrini
P R
PR
Plate
K H
KH
D042683:Angiopoietin-1; D042702:Angiopoietin-2; D000818:Animals; D017209:Apoptosis; D001157:Arterial Occlusive Diseases / Q000378:metabolism* / Q000503:physiopathology; D001808:Blood Vessels / Q000503:physiopathology; D002455:Cell Division; D002536:Cerebral Arteries; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D042810:Receptor, TIE-1; D042787:Receptor, TIE-2; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D042764:Receptors, TIE
D042683:Angiopoietin-1; D042702:Angiopoietin-2; C467629:Angpt1 protein, rat; D008562:Membrane Glycoproteins; D011506:Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D020794:Receptor Protein-Tyrosine Kinases; D042810:Receptor, TIE-1; D042787:Receptor, TIE-2; D042764:Receptors, TIE