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. METHODS AND 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.
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. METHODS AND 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.
Authors: Laura A Maile; Walker H Busby; Timothy C Nichols; Dwight A Bellinger; Elizabeth P Merricks; Michael Rowland; Umadevi Veluvolu; David R Clemmons Journal: Sci Transl Med Date: 2010-02-10 Impact factor: 17.956
Authors: Jeffrey A Spencer; Shelby L Hacker; Elaine C Davis; Robert P Mecham; Russ H Knutsen; Dean Y Li; Robert D Gerard; James A Richardson; Eric N Olson; Hiromi Yanagisawa Journal: Proc Natl Acad Sci U S A Date: 2005-02-14 Impact factor: 11.205
Authors: Manikandan Panchatcharam; Sumitra Miriyala; Fanmuyi Yang; Michael Leitges; Magdalena Chrzanowska-Wodnicka; Lawrence A Quilliam; Paul Anaya; Andrew J Morris; Susan S Smyth Journal: Int J Biochem Cell Biol Date: 2010-02-23 Impact factor: 5.085
Authors: Taku Kokubo; Noriyuki Ishikawa; Hisashi Uchida; Sara E Chasnoff; Xun Xie; Suresh Mathew; Keith A Hruska; Eric T Choi Journal: J Am Soc Nephrol Date: 2009-05-07 Impact factor: 10.121