Vitronectin is up-regulated after vascular injury and vitronectin blockade prevents neointima formation.
OBJECTIVE
Smooth muscle cell (SMC) migration involves interactions with extracellular matrix (ECM) and is an important process in response to arterial wall injury. We investigated the expression and the functional role of vitronectin (VN) in the response after vascular injury.


METHODS
VN and alpha v beta 3/beta 5 integrin expressions were investigated after balloon carotid injury of Sprague-Dawley rats. Adventitial delivery of blocking antibodies to VN, alpha v beta 5 and beta 3 integrins were performed to assess their roles in neointima formation. In vitro, migration assays were carried out on human SMC.


RESULTS
Immunohistochemistry and in situ hybridization for VN showed an upregulation of VN during the early time points of intima formation. alpha v beta 3/beta 5 integrins expression correlated with VN expression. After 7 days, blocking antibodies to VN, alpha v beta 5 and beta 3 induced a significant decrease on intimal area associated with a decrease in intimal cell counts. A slight decrease in intimal cell proliferation without any effect on apoptosis was observed after VN blockade. In vitro, migrating SMC strongly expressed VN after injury and neutralizing anti-VN antibody inhibited SMC migration. Blocking experiment with anti-alpha v beta 5 and -alpha v beta 3 integrin antibodies showed that not only VN-alpha v beta 3 but also VN-alpha v beta 5 interactions are required for SMC migration.


CONCLUSIONS
This study characterizes the VN-ECM interaction in SMC and supports the role of VN in mediating SMC migration and neointimal formation in response to injury.
Dufourcq
Pascale
P
Institut National de la Santé et de la Recherche Médicale, INSERM Unité 441, Athéroclérose, Avenue du Haut-Lévêque, 33600 Pessac, France. pascale.dufourcq@biophar.u-bordeaux2.fr
Couffinhal
Thierry
T
Alzieu
Philipe
P
Daret
Danièle
D
Moreau
Catherine
C
Duplàa
Cécile
C
Bonnet
Jacques
J
D000328:Adult; D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D020212:Carotid Artery Injuries / Q000209:etiology / Q000378:metabolism*; D016893:Carotid Stenosis / Q000628:therapy*; D002455:Cell Division; D002465:Cell Movement; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000037:antagonists & inhibitors / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019030:Receptors, Vitronectin / Q000378:metabolism; D012008:Recurrence; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation; D019096:Vitronectin / Q000037:antagonists & inhibitors / Q000378:metabolism*
D016023:Integrins; D019030:Receptors, Vitronectin; D019096:Vitronectin; C064660:integrin alphaVbeta5