Cellular and molecular biology of vascular remodeling.
The vascular system undergoes remodeling throughout life, first as primitive vessels form and reorganize, then as the circulation accommodates changing tissue perfusion requirements. Recent investigations that have targeted receptor tyrosine kinases have elucidated fundamental mechanisms that are involved in early formation and restructuring of blood vessels. Distinct receptors for vascular endothelial growth factor, and other receptor tyrosine kinases, appear to regulate very different aspects of early vessel formation including endothelial cell differentiation, tube formation and differentiation of blood vessels into microvasculature versus large vessels. In later development and in the adult circulation, remodeling adapts arteries to chronic changes in hemodynamic function. Furthermore, novel findings of how vascular cells transduce the hemodynamic forces to which they respond have been reported. Force-sensitive gene transcription occurs by previously characterized transcription factors that bind to both established and novel responsive elements in promoter regions of relevant genes. There now is evidence that more than one of these factors can regulate gene expression in response to a single physical force (shear stress). Recent studies have emphasized the role of matrix degradation and cell death, in addition to matrix synthesis and cell proliferation, in arterial remodeling. The importance of cell death and matrix degradation has also been emphasized in the pathogenesis of vascular pathologies. As a result of these and other findings, the role tissue remodeling is being examined closely as a primary factor in the pathogenesis of atherosclerosis, hypertension and restenosis after angioplasty.
Cowan
D B
DB
Vascular Research Laboratory, Toronto Hospital Research Institute, Ontario, Canada.
Langille
B L
BL
D000222:Adaptation, Physiological; D000328:Adult; D000818:Animals; D001158:Arteries / Q000473:pathology / Q000502:physiology; D001161:Arteriosclerosis / Q000473:pathology / Q000503:physiopathology; D001794:Blood Pressure / Q000502:physiology; D003251:Constriction, Pathologic; D005314:Embryonic and Fetal Development / Q000502:physiology; D004730:Endothelium, Vascular / Q000473:pathology / Q000502:physiology; D006801:Humans; D024510:Muscle Development; D009131:Muscle, Smooth, Vascular / Q000196:embryology / Q000254:growth & development / Q000473:pathology*