Beta3-integrin mediates smooth muscle cell accumulation in neointima after carotid ligation in mice.
BACKGROUND
Pharmacological blockade of beta3-integrins inhibits neointimal lesion formation in nonmouse animal models of arterial injury. In contrast, beta3-integrin-deficient (beta3-/-) mice are not protected from neointimal lesion formation after arterial injury. We investigated this discrepancy in beta3-/- and wild-type (beta3+/+) mice using different models of injury.


RESULTS
After disruption of the carotid with a transluminal probe, there was no significant difference in neointimal thickening between beta3-/- and beta3+/+ mice. However, after ligation of the carotid without medial disruption, there was reduced neointimal thickening in beta3-/- mice compared with beta3+/+ mice at intervals up to 3 months. Lesion reduction in beta3-/- mice was associated with fewer intimal smooth muscle cells (SMCs) without a difference in SMC apoptosis or proliferation rate compared with beta3+/+ mice, consistent with reduced SMC migration from the media into the intima of beta3-/- mice. Moreover, combined eccentric medial disruption and ligation of the carotid in beta3-/- mice resulted in neointimal lesion formation only at the site of medial disruption. Transplantation of bone marrow cells harvested from beta3+/+ mice into irradiated beta3-/- mice resulted in reduced neointimal lesion formation after carotid ligation injury, confirming the importance of alpha(v)beta3 and not alpha(IIb)beta3 in the attenuated response.


CONCLUSIONS
The alpha(v)beta3-integrin mediates intimal SMC accumulation that contributes to neointimal thickening in the setting of arterial ligation.
Department of Surgery, Washington University School of Medicine, St Louis, Mo, USA. choie@msnotes.wustl.edu
Eric T
ET
Choi
M Faisal
MF
Khan
Jeremy E
JE
Leidenfrost
Emily T
ET
Collins
Kenneth P
KP
Boc
Brian R
BR
Villa
Deborah V
DV
Novack
William C
WC
Parks
Dana R
DR
Abendschein
D000818:Animals; D017209:Apoptosis; D016026:Bone Marrow Transplantation; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D020212:Carotid Artery Injuries / Q000209:etiology / Q000473:pathology*; D016893:Carotid Stenosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division; D002465:Cell Movement; D002478:Cells, Cultured / Q000166:cytology / Q000378:metabolism; D002633:Chemotaxis; D004195:Disease Models, Animal; D006965:Hyperplasia; D039302:Integrin alphaVbeta3 / Q000502:physiology*; D039661:Integrin beta3 / Q000187:drug effects / Q000502:physiology*; D008026:Ligation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000473:pathology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000502:physiology; D011828:Radiation Chimera; D013314:Stress, Mechanical; D017539:Tunica Intima / Q000473:pathology*
D039302:Integrin alphaVbeta3; D039661:Integrin beta3; D019039:Platelet Glycoprotein GPIIb-IIIa Complex