From the Sealy Center for Molecular Cardiology (G.A.S., Z.H., M.S., H.L.,
G.J., M.S.R.), University of Texas Medical Branch, Galveston; Centocor, Inc
(M.T.N.), Malvern, Pa; and Yerkes Regional Primate Research Center and
Department of Medicine (S.R.H.), Emory University School of Medicine, Atlanta,
Ga.
Correspondence to George A. Stouffer, Route 1064, Medical Research Bldg, 301 University Blvd, University of Texas Medical Branch, Galveston, TX 77555-1064. E-mail stouffer{at}cardiology.utmb.edu
Background—Treatment with an
antibody that binds ß3 integrins (abciximab; c7E3 Fab) at
the time of coronary angioplasty decreases the need for repeat
revascularization. Two potential mechanisms have
been proposed to explain this effect: (1) inhibition of platelet
aggregation or (2) interruption of ligand binding to ß3
integrins on the smooth muscle cell (SMC) surface. We examined the
latter hypothesis by determining (1) if ß3 integrin
expression is upregulated after vascular injury in the baboon, (2) if
7E3 binds ß3 integrins on cultured SMC, and (3) if
ß3 integrin activation plays a role in proliferation of
cultured SMC.
Methods and Results—Results demonstrated that
immunostaining for ß3 integrins was
present in the neointima 1 week after balloon
withdrawal injury of baboon brachial arteries and that ß3
integrin expression colocalized with
Conclusions—In summary, these studies demonstrate that vascular
cell ß3 integrin expression is increased after injury,
that 7E3 binds to cultured SMC with high affinity, and that
ß3 activation is important for thrombospondin-induced or
© 1998 American Heart Association, Inc.
Basic Science Reports
ß3 Integrins Are Upregulated After Vascular Injury and Modulate Thrombospondin- and Thrombin-Induced Proliferation of Cultured Smooth Muscle Cells
-actin–positive cells. In
contrast, staining for ß3 integrins was undetectable in
contralateral uninjured brachial arteries. 7E3 bound to cultured human
aortic SMC with an affinity (KD=3.3 nmol/L)
similar to 7E3 binding to endothelial cells or
platelets. Cotreatment with 7E3 partially inhibited
thrombospondin-induced or -thrombin–induced proliferation but not
PDGF-induced or serum-induced proliferation. -thrombin–induced proliferation. These results support the
hypothesis that ß3 integrins play a role in SMC growth
responses after balloon injury.
Key Words: receptors • muscle, smooth • angioplasty • signal transduction
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