alphavbeta3, alphavbeta5, and osteopontin are coordinately upregulated at early time points in a rabbit model of neointima formation.
Both smooth muscle cell migration and replication are known to be responsible for neointima formation. Recent reports based on in vitro studies and animal models of neointima formation highlight the possible importance of alphavbeta3 and alphavbeta5 integrins in mediating neointima formation. Clinical data suggest that specific alphavbeta3 blockade may limit restenosis. The aim of this study was to identify the expression of alphavbeta3 and alphavbeta5 and their ligand osteopontin in the very early phases of neointima formation in a rabbit model. A non-occlusive cuff placed around the rabbit femoral artery resulted in a complete, concentric neointima that formed by 14 days. Antibodies specific for the integrin heterodimers and for osteopontin, along with a probe specific for osteopontin mRNA, were used to identify expression at early time points (6 h, 1 day, 3 days, 5 days) post-cuffing. Immunohistochemistry and in situ hybridization expression results were quantitated by image analysis and tested for statistical significance by a two-tailed t-test. The data demonstrated the rapid (within 6 h) and abundant upregulation of alphavbeta3 and alphavbeta5 integrins and their ligand during very early time points of neointima formation. The very early (6 h) upregulation of alphavbeta3 underscores a potentially important clinical intervention point in limiting restenosis following clinical angioplasty procedures.
Corjay
M H
MH
DuPont Pharmaceuticals Research Laboratories, Experimental Station, Wilmington, Delaware 19880-0440, USA. martha.h.corjay@dupontpharma.com
Diamond
S M
SM
Schlingmann
K L
KL
Gibbs
S K
SK
Stoltenborg
J K
JK
Racanelli
A L
AL
D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D016023:Integrins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D008024:Ligands; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D053495:Osteopontin; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D012008:Recurrence; D012795:Sialoglycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation
D016023:Integrins; D008024:Ligands; D012333:RNA, Messenger; D019030:Receptors, Vitronectin; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C064660:integrin alphaVbeta5; D053495:Osteopontin