Eptifibatide and 7E3, but Not Tirofiban, Inhibit α
            <sub>v</sub>
            β
            <sub>3</sub>
            Integrin–Mediated Binding of Smooth Muscle Cells to Thrombospondin and Prothrombin

Lele, Manjiri; Sajid, Muhammad Imran; Wajih, Nadeem; Stouffer, George A.

doi:10.1161/hc3101.092199

Cited by 76 publications

(50 citation statements)

References 35 publications

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“…This finding is consistent with previous results showing that only ␣ v ␤ 3 -integrin blockade and not ␣ IIb ␤ 3 -integrin blockade was effective in reducing SMC migration. 23,24 In summary, our data support the conclusion that ␣ v ␤ 3 plays a critical role in SMC migration and neointimal lesion formation. The effectiveness of ␤ 3 -integrin deficiency is dependent on the severity of vascular injury, with benefit exhibited after nondisruptive arterial wall injury but not with donor bone marrow (*PϽ0.01), indicating that ␤ 3 ϩ/ϩ bone marrow (ie, ␤ 3 -integrin-expressing platelets) did not contribute to the inhibitory effect of ␤ 3 -integrin deficiency.…”

Section: Discussionsupporting

confidence: 85%

β ₃ -Integrin Mediates Smooth Muscle Cell Accumulation in Neointima After Carotid Ligation in Mice

et al. 2004

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Background-Pharmacological blockade of ␤ 3 -integrins inhibits neointimal lesion formation in nonmouse animal models of arterial injury. In contrast, ␤ 3 -integrin-deficient (␤ 3 Ϫ/Ϫ ) mice are not protected from neointimal lesion formation after arterial injury. We investigated this discrepancy in ␤ 3 Ϫ/Ϫ and wild-type (␤ 3 ϩ/ϩ ) 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 ␤ 3 Ϫ/Ϫ and ␤ 3 ϩ/ϩ mice. However, after ligation of the carotid without medial disruption, there was reduced neointimal thickening in ␤ 3 Ϫ/Ϫ mice compared with ␤ 3 ϩ/ϩ mice at intervals up to 3 months. Lesion reduction in ␤ 3 Ϫ/Ϫ mice was associated with fewer intimal smooth muscle cells (SMCs) without a difference in SMC apoptosis or proliferation rate compared with ␤ 3 ϩ/ϩ mice, consistent with reduced SMC migration from the media into the intima of ␤ 3 Ϫ/Ϫ mice. Moreover, combined eccentric medial disruption and ligation of the carotid in ␤ 3 Ϫ/Ϫ mice resulted in neointimal lesion formation only at the site of medial disruption. Transplantation of bone marrow cells harvested from ␤ 3 ϩ/ϩ mice into irradiated ␤ 3 Ϫ/Ϫ mice resulted in reduced neointimal lesion formation after carotid ligation injury, confirming the importance of ␣ v ␤ 3 and not ␣ IIb ␤ 3 in the attenuated response. Conclusions-The ␣ v ␤ 3 -integrin mediates intimal SMC accumulation that contributes to neointimal thickening in the setting of arterial ligation.

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Section: Discussionsupporting

confidence: 85%

β ₃ -Integrin Mediates Smooth Muscle Cell Accumulation in Neointima After Carotid Ligation in Mice

et al. 2004

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“…SMC isolated from the aortas of SpragueDawley rats were cultured as previously described (11,18). Briefly, RASMC, passages 3-10, were grown to 70% subconfluence in serum-containing medium.…”

Section: Methodsmentioning

confidence: 99%

α_vβ₃-Integrin antagonists inhibit thrombin-induced proliferation and focal adhesion formation in smooth muscle cells

Sajid

Zhao

Pathak

et al. 2003

American Journal of Physiology-Cell Physiology

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Sajid, M., R. Zhao, A. Pathak, S. S. Smyth, and G. A. Stouffer. ␣ v␤3-Integrin antagonists inhibit thrombin-induced proliferation and focal adhesion formation in smooth muscle cells. Am J Physiol Cell Physiol 285: C1330-C1338, 2003. First published July 23, 2003 10.1152 10. /ajpcell.00475.2002tegrin antagonists reduced neointimal formation following vascular injury in eight different animal models. Because ␣-thrombin contributes to neointimal formation, we examined the hypothesis that ␣ v␤3-integrins influence ␣-thrombin-induced signaling. Cultured rat aortic smooth muscle cells (RASMC) expressed ␣ v␤3-integrins as demonstrated by immunofluorescence microscopy and fluorescence-activated cell sorting analysis. Proliferative responses to ␣-thrombin were partially inhibited by anti-␤ 3-integrin monoclonal antibody F11 and by cyclic RGD peptides. Immunofluorescence microscopy showed that ␣-thrombin stimulated a rapid increase in the formation of focal adhesions as identified by vinculin staining and that this effect was partially inhibited by ␣ v␤3 antagonists. ␤3-Integrin staining was diffuse in quiescent RASMC and did not concentrate at sites of focal adhesions following thrombin treatment. ␣-Thrombin elicited a time-dependent increase in activation of c-Jun NH 2-terminal kinase-1 (JNK1) and in tyrosine phosphorylation of focal adhesion kinase (FAK). ␣ v␤3-Integrin antagonists partially inhibited increases in JNK1 activity but had no effect on FAK phosphorylation. In SMC isolated from ␤ 3-integrin-deficient mice, focal adhesion formation was impaired in response to thrombin but not sphingosine-1-phosphate, a potent activator of Rho. In summary, ␣ v␤3-integrins play an important role in ␣-thrombin-induced proliferation and focal adhesion formation in RASMC.receptors; vitronectin; integrins; focal adhesions PERCUTANEOUS CORONARY INTERVENTION (PCI) involves application of a controlled injury to a coronary artery to relieve focal obstruction. The injury stimulates a healing response, which, when overexuberant, leads to renarrowing of the artery in a process labeled "restenosis." Animal models have implicated ␣ v ␤ 3 -integrins in playing an important role in vascular healing responses. Studies in baboons, rats, rabbits, and pigs have shown that balloon angioplasty is a stimulus for ␤ 3 -integrin expression by vascular smooth muscle cells (SMC) (6,21,23) and that treatment with ␣ v ␤ 3 antagonists reduces (neo)intima formation after vascular injury (reviewed in Ref. 19).␣ v ␤ 3 -Integrins influence responses of cultured SMC to many extracellular agonists that may be important in healing responses in injured blood vessels. In addition to inhibiting responses to agents that directly bind ␣ v ␤ 3 , such as thrombospondin and osteopontin (23,24,27), ␣ v ␤ 3 antagonists also regulate SMC responses to platelet-derived growth factor (3, 4), epidermal growth factor (10), insulin-like growth factor-I (9), transforming growth factor-␤ (18), and ␣-thrombin (24). ␣-Thrombin is of particular interest because it is concentrated at ...

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“…Previous studies have found that TSP-1-stimulated SMCs or ␤ 3 integrin-expressing HEK cell proliferation is significantly inhibited by ␣ v ␤ 3 integrin blocking reagents. 34,35 Because the suppression of TSP-1-induced proliferation by the reagents was partial, receptors other than ␣ v ␤ 3 integrin may also be involved in TSP-1-stimulated signals, leading to proliferation. Our data suggest that together with ␤ 3 integrin, ␤ 1 integrin also appears to be involved in TSP-1-stimulated cell proliferation.…”

mentioning

confidence: 99%

Thrombospondin-1 Mediates Smooth Muscle Cell Proliferation Induced by Interaction With Human Platelets

Ichii

Koyama

Tanaka

et al. 2002

ATVB

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Objectives-Platelet adherence and activation are associated with smooth muscle cell (SMC) proliferation and arterial restenosis. This study examined platelet-SMC interaction on fibrillar type I collagen and analyzed the role of thrombospondin (TSP)-1 in platelet-induced SMC proliferation. Methods and Results-When SMCs cultured on fibrillar collagen were treated with human platelets (5 preparations), 7.45Ϯ2.94% of the cells passed through S phase within 24 hours, as determined by bromodeoxyuridine nuclear labeling. The addition of platelets markedly induced SMC TSP-1 mRNA expression and cell surface protein accumulation, which colocalized with adhered platelets, as determined by ␣ IIb integrin immunostaining. Direct interaction of platelets with SMCs was necessary for its effect on proliferation and TSP-1 accumulation, as determined in the transwell culture system. The anti-TSP-1 blocking antibody strongly inhibited platelet-induced SMC proliferation by Ϸ60%. Analysis of the receptors for TSP-1 accumulation on the SMC surface revealed that ␤ 1 integrins are mainly involved. The anti-␤ 1 integrin blocking antibody, which potently suppressed TSP-1 accumulation on SMCs, also markedly inhibited platelet-stimulated SMC proliferation. Conclusions-TSP-1 and ␤ 1 integrin interaction is involved in platelet-stimulated SMC proliferation. This in vitro coculture system could prove useful for examining the molecular mechanism underlying platelet-induced vascular remodeling and for studying the mechanism of a tested drug for restenosis. Key Words: atherosclerosis Ⅲ platelet-derived factors Ⅲ integrins Ⅲ collagen (type I) Ⅲ vascular injury T he vascular endothelium plays a fundamental role in the local regulation of vascular tone and homeostasis. 1 Injury of a vascular segment elicits a complex sequence of events characterized by platelet adhesion and aggregation, leukocyte infiltration, and smooth muscle cell (SMC) migration and proliferation. 2,3 In experimental models, platelet aggregation and adhesion to the wall of injured vessels have been demonstrated in the early phase after balloon injury. 4 Even though platelets disappeared from the arterial surface within a few days after injury, initial platelet adhesions appear to play important roles in intimal lesion formation. 5 Platelet adherence and activation are associated with the local release of potent vasoactive factors, such as thrombin, platelet-derived growth factor (PDGF), transforming growth factor (TGF)-␤, insulin-like growth factor-I, and thromboxane A 2 . 6 These factors are known to stimulate the migration, proliferation, and synthesis of extracellular matrix molecules by SMCs that may lead to the development of an intimal lesion. However, the molecular mechanism behind the role of platelets in lesion formation is still not entirely clear. See coverThe matricellular protein thrombospondin (TSP)-1 is a 450-kDa homotrimeric glycoprotein that influences cell function by modulating cell-matrix interaction (see recent reviews 7,8 ). It is well known that TSP-1 is se...

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Eptifibatide and 7E3, but Not Tirofiban, Inhibit α _v β ₃ Integrin–Mediated Binding of Smooth Muscle Cells to Thrombospondin and Prothrombin

Cited by 76 publications

References 35 publications

β ₃ -Integrin Mediates Smooth Muscle Cell Accumulation in Neointima After Carotid Ligation in Mice

β ₃ -Integrin Mediates Smooth Muscle Cell Accumulation in Neointima After Carotid Ligation in Mice

α_vβ₃-Integrin antagonists inhibit thrombin-induced proliferation and focal adhesion formation in smooth muscle cells

Thrombospondin-1 Mediates Smooth Muscle Cell Proliferation Induced by Interaction With Human Platelets

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Eptifibatide and 7E3, but Not Tirofiban, Inhibit α v β 3 Integrin–Mediated Binding of Smooth Muscle Cells to Thrombospondin and Prothrombin

Cited by 76 publications

References 35 publications

β 3 -Integrin Mediates Smooth Muscle Cell Accumulation in Neointima After Carotid Ligation in Mice

β 3 -Integrin Mediates Smooth Muscle Cell Accumulation in Neointima After Carotid Ligation in Mice

αvβ3-Integrin antagonists inhibit thrombin-induced proliferation and focal adhesion formation in smooth muscle cells

Thrombospondin-1 Mediates Smooth Muscle Cell Proliferation Induced by Interaction With Human Platelets

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Eptifibatide and 7E3, but Not Tirofiban, Inhibit α _v β ₃ Integrin–Mediated Binding of Smooth Muscle Cells to Thrombospondin and Prothrombin

β ₃ -Integrin Mediates Smooth Muscle Cell Accumulation in Neointima After Carotid Ligation in Mice

β ₃ -Integrin Mediates Smooth Muscle Cell Accumulation in Neointima After Carotid Ligation in Mice

α_vβ₃-Integrin antagonists inhibit thrombin-induced proliferation and focal adhesion formation in smooth muscle cells