A comparative study of the antithrombotic effect of aurintricarboxylic acid on arterial thrombosis in rats and guinea‐pigs

Takiguchi, Yoshiharu; Shimazawa, Masamitsu; Nakashima, Mitsuyoshi

doi:10.1111/j.1476-5381.1996.tb15585.x

Cited by 11 publications

(6 citation statements)

References 24 publications

(29 reference statements)

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“…We previously reported a simple and reproducible thrombus model in the rat femoral artery, by endothelial denudation using a photochemical reaction between rose bengal and green light (540 nm). Direct injury to vessels was not observed by this application and platelet-rich thrombus was produced by endothelial damage without alteration of medial smooth muscle cells (12)(13)(14). This model was adapted to mouse carotid arteries, and applied to the investigation of the role of fibrinolytic system components on thrombus and removal, using gene-inactivated mice with deficiencies of u-PA, t-PA or PAI-1.…”

Section: Introductionmentioning

confidence: 99%

Differential Role of Components of the Fibrinolytic System in the Formation and Removal of Thrombus Induced by Endothelial Injury

Matsuno¹,

Kozawa²,

Niwa³

et al. 1999

Thromb Haemost

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SummaryThe role of fibrinolytic system components in thrombus formation and removal in vivo was investigated in groups of six mice deficient in urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA), or plasminogen activator inhibitor-1 (PAI-1) (u-PA-/-, t-PA-/- or PAI-1-/-, respectively) or of their wild type controls (u-PA+/+, t-PA+/+ or PAI-1+/+). Thrombus was induced in the murine carotid artery by endothelial injury using the photochemical reaction between rose bengal and green light (540 nm). Blood flow was continuously monitored for 90 min on day 0 and for 20 min on days 1, 2 and 3. The times to occlusion after the initiation of endothelial injury in u-PA+/+, t-PA+/+ or PAI-1+/+ mice were 9.4 ± 1.3, 9.8 ± 1.1 or 9.7 ± 1.6 min, respectively. u-PA-/- and t-PA-/- mice were indistinguishable from controls, whereas that of PAI-1-/- mice were significantly prolonged (18.4 ± 3.7 min). Occlusion persisted for the initial 90 min observation period in 10 of 18 wild type mice and was followed by cyclic reflow and reocclusion in the remaining 8 mice. At day 1, persistent occlusion was observed in 1 wild type mouse, 8 mice had cyclic reflow and reocclusion and 9 mice had persistent reflow. At day 2, all injured arteries had persistent reflow. Persistent occlusion for 90 min on day 0 was observed in 3 u-PA-/-, in all t-PA-/- mice at day 1 and in 2 of the t-PA-/-mice at day 2 (p <0.01 versus wild type mice). Persistent patency was observed in all PAI-1-/- mice at day 1 and in 5 of the 6 u-PA-/- mice at day 2 (both p <0.05 versus wild type mice). In conclusion, t-PA increases the rate of clot lysis after endothelial injury, PAI-1 reduces the time to occlusion and delays clot lysis, whereas u-PA has little effect on thrombus formation and spontaneous lysis.

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Section: Introductionmentioning

confidence: 99%

Differential Role of Components of the Fibrinolytic System in the Formation and Removal of Thrombus Induced by Endothelial Injury

Matsuno¹,

Kozawa²,

Niwa³

et al. 1999

Thromb Haemost

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“…It is thought that ATA is a useful prototype agent for inhibiting arterial thrombosis in vivo because ATA has been proven advantageous in the animal models of induced stenosis and vessel injury [15,19]. In the present study, we demonstrated a new antithrombotic effect of ATA: the dye compound ATA upregulated the surface thrombomodulin expression of endothelial cells and monocytes in a dose-dependent and time-dependent manner, and increased the mRNA level of endothelial thrombomodulin.…”

Section: Discussionmentioning

confidence: 69%

Aurintricarboxylic acid upregulates the thrombomodulin expression of endothelial cells and peripheral blood monocytes

Kim¹,

Kim²,

Park³

et al. 2008

Blood Coagulation & Fibrinolysis

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Thrombomodulin has a central role in the regulation of coagulation through its ability to promote generation of the potent anticoagulant, activated protein C. Aurintricarboxylic acid (ATA) has been reported to inhibit platelet function by blocking von Willebrand factor binding to platelet glycoprotein Ib and to impede thrombosis development in vivo. In the present study, we demonstrated a novel antithrombotic effect of ATA. The surface thrombomodulin expression of endothelial cells and peripheral blood monocytes was upregulated by ATA in a dose-dependent and time-dependent manner. ATA also increased the mRNA level of endothelial thrombomodulin in a dose-dependent manner. Tumor necrosis factor (TNF)-alpha (50 ng/ml) or lipopolysaccharide (20 microg/ml) downregulated the expression of endothelial thrombomodulin. Blocking of nuclear factor-kappaB by parthenolide effectively inhibited the TNF-alpha-induced thrombomodulin downregulation of endothelial cells. ATA increased endothelial thrombomodulin expression that was downregulated by TNF-alpha or lipopolysaccharide, in a dose-dependent manner. The inhibition of small G proteins of the Rho family by the Clostridium difficile toxin B-1,0643 did not increase thrombomodulin expression of endothelial cells, and ATA did not activate Rac1 in endothelial cells. These findings provide, at least in part, a novel platelet-independent mechanism of ATA that may explain the demonstrated antithrombotic efficacy of ATA.

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“…It is considered that ATA is a useful prototype agent for inhibiting arterial thrombosis in vivo because ATA has been proven to be advantageous in the animal models of induced stenosis and vessel injury [12,13]. ATA also inhibit endothelial apoptosis induced by oxidized low-density lipoprotein [14].…”

Section: Introductionmentioning

confidence: 99%

Aurintricarboxylic acid inhibits the nuclear factor-κB-dependent expression of intercellular cell adhesion molecule-1 and endothelial cell selectin on activated human endothelial cells

Kim¹,

Lee

Han³

et al. 2011

Blood Coagulation &Amp; Fibrinolysis

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Activation of the vascular endothelium and increased adhesion of circulating leukocytes to the activated endothelium are important events in inflammation and coagulation. Aurintricarboxylic acid (ATA), a triphenylmethyl dye compound, is known to inhibit platelet adhesion by interfering with the binding of von Willebrand factor to platelet glycoprotein Ib. However, the effect of ATA on the inflammatory response of endothelial cells has not yet been investigated. Here, we investigated the functional role and molecular mechanism of ATA on the activation of human endothelial cells. ATA inhibited the expression of intercellular adhesion molecule-1 (ICAM-1), and endothelial cell selectin (E-selectin) was upregulated on human umbilical vein endothelial cells (HUVECs) in response to tumor necrosis factor-α or lipopolysaccharide (LPS). We also observed the inhibitory effect of ATA on LPS-induced mRNA expression of ICAM-1 and E-selectin. Furthermore, ATA inhibited the binding of leukocytes to activated HUVECs. ATA significantly inhibited the nuclear translocation of nuclear factor-κB (NF-κB) and degradation of IκB on activated HUVECs, suggesting that ATA inhibits NF-κB signaling. Finally, three NF-κB inhibitors effectively inhibited the expressions of ICAM-1 and E-selectin on activated endothelial cells. The present data suggest that ATA exerts beneficial effect in various inflammation conditions through inhibition of adhesion molecule expression in activated endothelial cells and the resulting inhibition of leukocytes tissue accumulation.

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A comparative study of the antithrombotic effect of aurintricarboxylic acid on arterial thrombosis in rats and guinea‐pigs

Cited by 11 publications

References 24 publications

Differential Role of Components of the Fibrinolytic System in the Formation and Removal of Thrombus Induced by Endothelial Injury

Differential Role of Components of the Fibrinolytic System in the Formation and Removal of Thrombus Induced by Endothelial Injury

Aurintricarboxylic acid upregulates the thrombomodulin expression of endothelial cells and peripheral blood monocytes

Aurintricarboxylic acid inhibits the nuclear factor-κB-dependent expression of intercellular cell adhesion molecule-1 and endothelial cell selectin on activated human endothelial cells

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