title: A disintegrin and metalloprotease 17 mediates neointimal hyperplasia in vasculature.
abstract: The requirement of a metalloprotease, a disintegrin and metalloprotease 17 (ADAM17) for the growth of cultured vascular smooth muscle cells has been demonstrated in vitro. However, whether this metalloprotease is responsible for vascular remodeling in vivo remains unanswered. Rat carotid arteries were analyzed 2 weeks after a balloon angioplasty. The neointimal cells were strongly positive for ADAM17 immunostaining. Marked inhibition of intimal hyperplasia was observed in a dominant-negative ADAM17 adenovirus-treated carotid artery. Proliferating cell nuclear antigen-positive cells and phospho-epidermal growth factor receptor-positive cells in the neointima were reduced by dominant-negative ADAM17 as well. In contrast, the neointima formation, proliferating cell nuclear antigen-positive cells, and phospho-epidermal growth factor receptor-positive cells were markedly enhanced by wild-type ADAM17 adenovirus. In conclusion, ADAM17 activation is involved in epidermal growth factor receptor activation and subsequent neointimal hyperplasia after vascular injury. ADAM17 could be a novel therapeutic target for pathophysiological vascular remodeling.
authors.affiliation: Cardiovascular Research Center, Temple University School of Medicine, 3500 N Broad St, Philadelphia, PA 19140, USA.
authors.forename: Akira
authors.initials: A
authors.lastname: Takaguri
authors.forename: Keita
authors.initials: K
authors.lastname: Kimura
authors.forename: Akinari
authors.initials: A
authors.lastname: Hinoki
authors.forename: Allison M
authors.initials: AM
authors.lastname: Bourne
authors.forename: Michael V
authors.initials: MV
authors.lastname: Autieri
authors.forename: Satoru
authors.initials: S
authors.lastname: Eguchi
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism*; D000072198:ADAM17 Protein; D000800:Angioplasty, Balloon; D000818:Animals; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology*; D020212:Carotid Artery Injuries / Q000378:metabolism* / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D066246:ErbB Receptors / Q000378:metabolism; D006965:Hyperplasia / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D058426:Neointima / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D066246:ErbB Receptors; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606464:Adam17 protein, rat