The urokinase receptor mediates basic fibroblast growth factor-dependent smooth muscle cell migration through baboon aortic explants

• Published in: Atherosclerosis 2002-05, Vol.162 (1), p.63-67
• Main Authors: Kenagy, R.D., Vesti, B.R., Clowes, A.W.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Blocking - pharmacology; Aorta, Thoracic - cytology; Aorta, Thoracic - metabolism; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cell Movement - drug effects; Dose-Response Relationship, Immunologic; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Enzyme Activation - drug effects; Fibroblast growth factor; Fibroblast Growth Factor 2 - drug effects; Fibroblast Growth Factor 2 - physiology; Matrix Metalloproteinase 2 - drug effects; Medical sciences; Migration; Models, Animal; Models, Cardiovascular; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Papio; Plasminogen Activators - drug effects; Plasminogen Activators - physiology; Primate; Receptors, Cell Surface - drug effects; Receptors, Cell Surface - physiology; Receptors, Urokinase Plasminogen Activator; Smooth muscle; Urokinase receptor; Urokinase-Type Plasminogen Activator - drug effects; Urokinase-Type Plasminogen Activator - physiology
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/S0021-9150(01)00682-7

The urokinase receptor is required for vascular smooth muscle cell migration in vitro, but may not be needed in vivo since smooth muscle cell migration and intimal hyperplasia after arterial injury in mice are not affected by urokinase receptor gene deletion. We have used baboon aortic explants as a bridge between cell culture and in vivo experiments to determine if the urokinase receptor is required for smooth muscle cell proliferation and smooth muscle cell migration in primate vessels. Levels of urokinase receptor in explants increased with time after explantation, while blockade of urokinase receptor with an antibody decreased smooth muscle cell proliferation and smooth muscle cell migration from the explants. A blocking antibody to basic fibroblast growth decreased levels of urokinase and urokinase receptor in explants, and it decreased smooth muscle cell migration and mitogenesis. These results suggest that the factor urokinase receptor plays a positive role in smooth muscle cell migration and proliferation in injured primate arterial tissue, in part mediating the pro-migratory and proliferative effects of basic fibroblast growth factor released by damaged smooth muscle cells.