Ischemia/angiogenesis-related molecules and cells

Abstract

Twenty-three fibroblast growth factors (FGFs) and four tyrosine kinase receptors (FGFRs) have been identified. FGF-1 and FGF-2 are potent stimulators of endothelial cell proliferation, migration, sprouting, and tube formation and bind to all four FGFRs [1] (Table 1). Ten isoforms have been identified in the brain. In particular, FGF-2 increases the expression of the vascular endothelial growth factor (VEGF) and proteases, and upregulates the expression of αvβ3 integrin complexes and other adhesion molecules in endothelial cells. Sections of the superficial temporal artery (STA) from patients with moyamoya disease (MMD) exhibit dense and strong FGFR signal and basic FGF immunoreactivity in endothelial cells, in cells scattered in the thickened intima, and in smooth muscle cells (SMCs) in the media [2]. It is reported that FGF-2 is also elevated (by ~tenfold) in the cerebrospinal fluid (CSF) of patients with MMD and is also increased in patients with good outcomes after surgical revascularization [3, 4]. The upregulation of FGF-2 can be interpreted as either promoting collateral vascularization or as the causative agent in progressive stenosis. FGF-4 has been demonstrated to increase the production of matrix metalloproteases 1 (MMP-1) and to decrease the levels of the tissue inhibitor of MMP-1 (TIMP-1) via the upregulation of VEGF by FGF-4. © 2010 Springer-Verlag Tokyo.