Insulin-like growth factor I is required for vessel remodeling in the adult brain.
Although vascular dysfunction is a major suspect in the etiology of several important neurodegenerative diseases, the signals involved in vessel homeostasis in the brain are still poorly understood. We have determined whether insulin-like growth factor I (IGF-I), a wide-spectrum growth factor with angiogenic actions, participates in vascular remodeling in the adult brain. IGF-I induces the growth of cultured brain endothelial cells through hypoxiainducible factor 1 alpha and vascular endothelial growth factor, a canonical angiogenic pathway. Furthermore, the systemic injection of IGF-I in adult mice increases brain vessel density. Physical exercise that stimulates widespread brain vessel growth in normal mice fails to do so in mice with low serum IGF-I. Brain injury that stimulates angiogenesis at the injury site also requires IGF-I to promote perilesion vessel growth, because blockade of IGF-I input by an anti-IGF-I abrogates vascular growth at the injury site. Thus, IGF-I participates in vessel remodeling in the adult brain. Low serum/brain IGF-I levels that are associated with old age and with several neurodegenerative diseases may be related to an increased risk of vascular dysfunction.
Lopez-Lopez
C
C
Laboratory of Neuroendocrinology, Cajal Institute, Consejo Superior de Investigaciones Cientifícas, 28002 Madrid, Spain.
LeRoith
D
D
Torres-Aleman
I
I
D000375:Aging / Q000502:physiology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001921:Brain / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D001930:Brain Injuries / Q000473:pathology / Q000503:physiopathology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000172:deficiency / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010805:Physical Conditioning, Animal / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D044967:Serum / Q000737:chemistry
D000906:Antibodies; D007334:Insulin-Like Growth Factor I