Time- and cell type-specific induction of platelet-derived growth factor receptor-beta during cerebral ischemia.
During cerebral ischemia, angiogenesis occurs inside and around the infarcted area. The growth of new blood vessels may contribute to a better outcome after stroke due to accelerated and increased delivery of nutrients and oxygen to the ischemic tissue. The platelet-derived growth factor (PDGF)-B/PDGF receptor (PDGFR)-beta system, hitherto thought to contribute mainly to neuroprotection, may also support angiogenesis and vascular remodeling by mediating interactions of endothelial cells with pericytes after cerebral ischemia. While platelet-derived growth factor (PDGF)-B and its receptor PDGFR-beta are essential factors for the recruitment of pericytes to brain capillaries during embryonic development, their role in blood vessel maturation during cerebral ischemia is not clear. The aim of the present study was to investigate the time course and location of PDGF-B and PDGFR-beta expression in a mouse model of focal cerebral ischemia. In contrast to the early and continuous induction of PDGF-B, PDGFR-beta mRNA was specifically upregulated in vascular structures in the infarcted area 48 h after occlusion of the middle cerebral artery. Immunohistology and confocal microscopy analysis revealed the specific upregulation of PDGFR-beta on blood vessels and suggested expression mainly on pericytes. Our results imply PDGFR-beta as a key factor in vascular remodeling during stroke and suggest that the pleiotropic functions of PDGF-B may be regulated via the expression of its receptor. Influencing the PDGF system therapeutically might improve angiogenesis, cellular protection, and edema inhibition.
Department of Experimental Cardiology, Max-Planck-Institute for Physiological and Clinical Research, D-61231 Bad Nauheim, Germany. orenner@cnio.es
Oliver
O
Renner
Asterios
A
Tsimpas
Sawa
S
Kostin
Samuel
S
Valable
Edwige
E
Petit
Wolfgang
W
Schaper
Hugo H
HH
Marti
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D002544:Cerebral Infarction / Q000235:genetics / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D051379:Mice; D008815:Mice, Inbred Strains; D018919:Neovascularization, Physiologic / Q000502:physiology*; D020286:Pericytes / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011930:Reaction Time / Q000235:genetics; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D020127:Recovery of Function / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics
D019408:Platelet Endothelial Cell Adhesion Molecule-1; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D020797:Receptor, Platelet-Derived Growth Factor beta