Effects of abciximab and tirofiban on vitronectin receptors in human endothelial and smooth muscle cells

Kintscher, Ulrich; Kappert, Kai; Schmidt, Günther; Doerr, Gesine; Grill, Matthias; Wollert-Wulf, Brigitte; Graefe, M.; Fleck, Eckart; Graf, Kristof

doi:10.1016/s0014-2999(99)00912-7

Cited by 19 publications

(15 citation statements)

References 41 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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“…These results are consistent with previous studies of human aortic 21 and human iliac 22 SMCs in which 7E3 at concentrations of 20 and 60 g/mL had no effect on adhesion to vitronectin. Similarly, neither 7E3 nor eptifibatide had any effect on HASMC attachment to collagen-or fibronectin-coated or noncoated tissue culture plates ( Figure 3B).…”

Section: Inhibitory Effects Of 7e3 and Eptifibatide But Not Tirofibasupporting

confidence: 93%

“…The inhibitory effects of eptifibatide (30 mol/L) and 7E3 were similar in magnitude (54% and 57%, respectively) and not additive. Endothelial cells, in contrast to SMCs, adhere to vitronectin via ␣ v ␤ 3 , 15,22 and we found that eptifibatide inhibited endothelial cell attachment to vitronectin by 30Ϯ9% (PϽ0.05 compared with control), an effect that was the same in magnitude as that observed with 7E3 (40Ϯ8%; PϽ0.05 compared with control; PϭNS, eptifibatide versus 7E3).…”

Section: Eptifibatide Inhibited Huvec Attachment To Tsp and Vitronectinsupporting

confidence: 60%

“…Our results are consistent with those of previous studies that found that tirofiban at a concentration of 120 mol/L did not block HUVEC attachment to or spreading on vitronectin. 22 The different affinities of eptifibatide and tirofiban for ␣ v ␤ 3 are not surprising, given that eptifibatide is a synthetic, cyclic peptide with a Lys-Gly-Asp (KGD) sequence, whereas tirofiban is a nonpeptide derivative of tyrosine.…”

Section: Lele Et Al Effects Of Gp Iib/iiia Inhibitors On Vascular Celmentioning

confidence: 99%

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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

et al. 2001

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Background-Our objective was to determine whether abciximab, eptifibatide, or tirofiban inhibited ligand binding to ␣ v ␤ 3 integrins on human aortic smooth muscle cells (HASMCs) or human umbilical vein endothelial cells (HUVECs). Abciximab binds ␣ IIb ␤ 3 on platelets and ␣ v ␤ 3 on HUVECs with similar affinity, whereas eptifibatide and tirofiban are thought to be highly specific for ␣ IIb ␤ 3 . The conclusion that eptifibatide does not bind vascular ␣ v ␤ 3 integrins may be premature, however, because recent studies have demonstrated that the affinity of ␣ v ␤ 3 for various ligands, including antagonists, is subject to modulation. Methods and Results-Abciximab and 7E3, the anti-␤ 3 integrin monoclonal antibody from which abciximab was derived, bound ␣ v ␤ 3 on HASMCs in a specific and saturable manner and with an affinity similar to binding to ␣ IIb ␤ 3 on platelets. 7E3 and eptifibatide inhibited ␣ v ␤ 3 -mediated attachment of HASMCs to thrombospondin (TSP) and prothrombin but had no effect on ␣ v ␤ 5 -or ␤ 1 -mediated HASMC attachment to vitronectin-, collagen-, or fibronectin-coated or noncoated tissue culture plates. The inhibitory effect of eptifibatide was similar in magnitude and not additive to that of 7E3.

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“…However, these studies were all performed in clinical settings where there was obvious endothelial damage, and the vascular effects of tirofiban on an intact endothelium is uncertain. Kintscher et al [32] found that tirofiban had no direct effect on cultured human vascular endothelial cells and suggested that it acts on the endothelium via indirect mechanisms. In this study, we observed no statistically significant difference in the dilation response between the control and tirofiban groups at any given concentration of Ach.…”

Section: Discussionmentioning

confidence: 99%

The effects of clopidogrel, acetyl salicylic acid and tirofiban on acetylcholine-induced dilation in rat thoracic aorta segments

Özkısacık¹,

Discigil²,

Kurtoğlu³

et al. 2012

Turk Gogus Kalp Dama

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Amaç: Bu çalışmada, asetilsalisilik asit (ASA), klopidogrel ve tirofiban gibi antitrombositer ajanların sıçan torasik aort segmentinde asetilkolin (ACh) ile uyarılan gevşeme yanıt-ları üzerine olan etkileri araştırıldı. Ça lış ma pla nı: Yirmi sekiz adet ağırlıkları 250-300 g arasında olan Wistar-albino türü yetişkin erkek sıçan çalışmaya alındı. Sıçanlar randomize olarak dört gruba ayrıldı: ASA grubu (n=7), klopidogrel grubu (n=7), tirofiban grubu (n=7) ve kontrol grubu (n=7). Deneyden 12 saat önce intraperitoneal (İP) ASA (1.5 mg/kg) veya klopidogrel (1 mg/kg) enjeksiyonları yapıldı. Tirofiban grubunda, 150 μgr/kg tirofiban İP deneyden 1 ve 12 saat önce olmak üzere, iki kez verildi. Kontrol grubundaki sıçanlara herhangi bir ilaç verilmedi. Sıçanlar dekapite edildikten sonra torasik aort segmentleri çıkartıldı ve oksijenize Krebs çözeltisi içinde organ banyosuna asıldı ve aort halkalarında asetilkolin ile uyarılan gevşeme yanıtının doza bağımlı değişimleri incelendi. Bul gu lar: Asetilkolinin en düşük molar konsantrasyonu (10-9) ile elde edilen gevşeme yanıtının ASA (%94.3±3.3) ve klopidogrel (%94.6±3.1) grubunda kontrol (%86.7±8.1) grubuna göre azalmış olduğu bulundu (p<0.05). Daha yük-sek asetilkolin konsantrasyonlarında ise, tüm gruplarda gevşeme yanıtlarının benzer olduğu gözlemlendi. So nuç: Asetilsalisilik asit ve klopidogrel tedavilerinin sonucunda endotel aracılı gevşeme yanıtında hafif bir gecikme ortaya çıkmış ve tirofibanın belirgin bir etkisi olmamıştır. Bu bulgular ASA ve klopidogrelin endotel aracılı vazodilatasyon üzerinde sınırlı bir etkisi olabileceğini düşündürmektedir.Anah tar söz cük ler: Asetilsalisilik asit; klopidogrel; endotel; tirofiban. Background:In this article, we aimed to investigate the effects of antithrombotic agents, including acetyl salicylic acid (ASA), clopidogrel, and tirofiban on the acetylcholine (ACh)-induced dilation responses in rat thoracic aorta segments. Methods: Twenty-eight Wistar albino male rats weighing between 250-300 g were included in the study. The rats were randomly divided into four groups: the ASA group (n=7), the clopidogrel group (n=7), the tirofiban group (n=7), and the control group (n=7). Intraperitoneal (IP) injection of ASA (1.5 mg/kg) or clopidogrel (1 mg/kg) was administered 12 hours before the experiment. In the tirofiban group, 150 μgr/kg tirofiban IP was given twice at one and 12 hours before the experiment. The rats in the control group did not receive any medication. After the rats were decapitated, the segments of the thoracic aorta were removed and suspended in an oxygenated Krebs solution in a tissue bath, and the dose dependency in the responses to the ACh-induced dilation in the aortic rings were studied. Results:The dilation responses of the aortic rings to ACh in the lowest molar concentration (10-9) were found to be reduced in the ASA (94.3%±3.3) and clopidogrel (94.6%±3.1) groups when compared with the control group (86.7%±8.1) (p<0.05). The responses to higher concentrations of ACh were observed to be similar in all of the groups....

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Effects of abciximab and tirofiban on vitronectin receptors in human endothelial and smooth muscle cells

Cited by 19 publications

References 41 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

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

The effects of clopidogrel, acetyl salicylic acid and tirofiban on acetylcholine-induced dilation in rat thoracic aorta segments

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Effects of abciximab and tirofiban on vitronectin receptors in human endothelial and smooth muscle cells

Cited by 19 publications

References 41 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

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

The effects of clopidogrel, acetyl salicylic acid and tirofiban on acetylcholine-induced dilation in rat thoracic aorta segments

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Product

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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

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