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(Circulation. 2004;109:1564-1569.)
© 2004 American Heart Association, Inc.

Basic Science Reports

ß₃-Integrin Mediates Smooth Muscle Cell Accumulation in Neointima After Carotid Ligation in Mice

Eric T. Choi, MD; M. Faisal Khan, MD; Jeremy E. Leidenfrost, BA; Emily T. Collins, BS; Kenneth P. Boc, BS; Brian R. Villa, BA; Deborah V. Novack, MD; William C. Parks, PhD; Dana R. Abendschein, PhD

From the Departments of Surgery (E.T.C., J.E.L., E.T.C., K.P.B., B.R.V.), Internal Medicine (M.F.K., D.R.A.), Pediatrics (W.C.P.), Cell Biology and Physiology (W.C.P., D.R.A.), and Pathology (D.V.N.), Washington University School of Medicine, St Louis, Mo.

Correspondence to Eric T. Choi, MD, 660 S Euclid Ave, Campus Box 8109, St Louis, MO 63110. E-mail choie{at}msnotes.wustl.edu

Received September 3, 2002; de novo received September 2, 2003; revision received December 1, 2003; accepted December 4, 2003.

Background— Pharmacological blockade of ß₃-integrins inhibits neointimal lesion formation in nonmouse animal models of arterial injury. In contrast, ß₃-integrin–deficient (ß₃^-/-) mice are not protected from neointimal lesion formation after arterial injury. We investigated this discrepancy in ß₃^-/- and wild-type (ß₃^+/+) mice using different models of injury.

Methods and Results— After disruption of the carotid with a transluminal probe, there was no significant difference in neointimal thickening between ß₃^-/- and ß₃^+/+ mice. However, after ligation of the carotid without medial disruption, there was reduced neointimal thickening in ß₃^-/- mice compared with ß₃^+/+ mice at intervals up to 3 months. Lesion reduction in ß₃^-/- mice was associated with fewer intimal smooth muscle cells (SMCs) without a difference in SMC apoptosis or proliferation rate compared with ß₃^+/+ mice, consistent with reduced SMC migration from the media into the intima of ß₃^-/- mice. Moreover, combined eccentric medial disruption and ligation of the carotid in ß₃^-/- mice resulted in neointimal lesion formation only at the site of medial disruption. Transplantation of bone marrow cells harvested from ß₃^+/+ mice into irradiated ß₃^-/- mice resulted in reduced neointimal lesion formation after carotid ligation injury, confirming the importance of _vß₃ and not _IIbß₃ in the attenuated response.

Conclusions— The _vß₃-integrin mediates intimal SMC accumulation that contributes to neointimal thickening in the setting of arterial ligation.

Key Words: restenosis • cell adhesion molecules • muscle, smooth • angioplasty

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