Mj. Slepian et al., BETA(3)-INTEGRINS RATHER THAN BETA(1)-INTEGRINS DOMINATE INTEGRIN-MATRIX INTERACTIONS INVOLVED IN POSTINJURY SMOOTH-MUSCLE CELL-MIGRATION, Circulation, 97(18), 1998, pp. 1818-1827
Citations number
52
Categorie Soggetti
Peripheal Vascular Diseas",Hematology,"Cardiac & Cardiovascular System
Background-Smooth muscle cell (SMC) migration is a vital component in
the response of the arterial wall to revascularization injury. Cell su
rface integrin-extracellular matrix interactions are essential for cal
l migration. SMCs express both beta(1)- and beta(3)-integrins. In this
study, we examined the relative functional roles of beta(1)- and beta
(3)-integrin-matrix interactions in postinjury SMC mi,oration. Methods
and Results-Flow cytometry and fluorescence microscopy of migrating S
MCs immunostained with anti-Pi and anti-alpha(v) beta(3/5) antibodies
(Abs) revealed expression of both beta(1)- and beta(3)-integrins, with
beta(1) observed as linear streaks and beta(3) found in focal contact
s. In a scrape-wound migration assay, anti-beta(1) Abs (92.0 +/- 10.7%
of control, P=.1) and 0.5 mmol/L linear RGD (105+/-5% of control, P=.
2) did not alter SMC migration at 48 hours after injury. beta(3)-Block
ade, however, via Abs (anti-beta(3/5) 35.7+/-4.5% of control, anti-bet
a(3) 61+/-12% of control, both P<.001) and cyclic RGD (0.5 mmol/L) (12
+/-10% of control, P<.001) decreased migration. Neither beta(1)- nor b
eta(3)-inhibition altered postinjury [H-3]thymidine incorporation. In
the rat carotid injury model, local adventitial polymer-based delivery
of radiolabeled linear or cyclic RGD led to uptake and retention of l
abel, for both peptides, over a 72-hour period after injury. Local art
erial wall beta(1)-blockade via polymer-based delivery of Linear RGD h
ad no effect on SMC migration at 4.5 days (11.5+/-3.2 versus 12.8 SMCs
per X600 field [control], P=.6) or on neointimal thickening at 14 day
s (I/M area ratio, 0.664+/-0.328 versus 1.179+/-0.324 [control], P=.6)
after injury. In contrast, local beta(3)-blockade via cRGD limited mi
gration (0.8+/-0.8 versus 12.8+/-4.4 SMCs per X600 field [control], P<
.01) and thickening (J/M area ratio, 0.004+/-0.008 versus 1.179+/-0.32
4 [control], P<.01). Conclusions-In postinjury migrating SMCs, beta(3)
- rather than beta(1)-integrin-matrix interactions are of greater func
tional significance in adhesive processes essential for SMC migration
in vitro and in vivo. Blockade of dominant SMC integrin (beta(3))-matr
ix interactions may be a valuable approach for limiting injury-induced
SMC migration and late arterial renarrowing.