scholarly journals In Vivo Fibrinopeptide a Generation Induced by Angiographic Catheters

1977 ◽  
Author(s):  
G. D. Wilner ◽  
W. J. Casarella ◽  
C. Fenoglio ◽  
R. E. Baier
Keyword(s):  
Thrombus Formation ◽  
Experimental Period ◽  
Fibrinopeptide A ◽  
Fibrin Deposition ◽  
Prosthetic Devices ◽  
Group Iii ◽  
Group I ◽  
Minute Period ◽  
Platelet Deposition

The use of fibrinopeptide A (FPA) levels to assess the hemostatic biocompatibility of prosthetic devices has been evaluated. Commercial angiographic catheters (7 French) of 5 different materials were introduced percutaneously 10 cm retrograde into the femoral arteries of anesthetized mongrel dogs. Catheter lumens were continually flushed with saline (1 ml/min). At intervals over a 30 minute period, saline flow was stopped and blood samples were withdrawn through the catheter lumen for FPA assay. Clot formation in catheter lumens was evaluated by scanning electron microscopy (SEM). The catheters could be divided into three groups based on FPA level generated and deposition of fibrin and platelets in the lumen. Group I (the PERT catheter) caused no increase in FPA (mean level 0.5 pmol/ml, equal to the level in the absence of any catheter), no fibrin deposition, and moderate platelet deposition. Group II (Torcon and Teflon catheters) caused moderate FPA generation (mean 7.1 pmol/ml), moderate fibrin deposition, and moderate platelet deposition. Group III catheters (polyurethane and Dacron) caused marked FPA generation (mean 26.2 pmol/ml), marked fibrin deposition, but variable platelet deposition. Thus mean FPA levels over the 30 minute experimental period correlated well with intraluminal fibrin deposition; FPA measurements should be useful in assessing the degree to which different catheters stimulate fibrin formation. FPA levels did not correlate with intraluminal platelet deposition and thus will not reflect platelet contributions to thrombus formation.

Role of leucine and other amino acids in regulating protein metabolism in vivo

1992 ◽  
Vol 262 (6) ◽  
pp. E925-E935 ◽  
Author(s):  
M. Frexes-Steed ◽  
D. B. Lacy ◽  
J. Collins ◽  
N. N. Abumrad
Keyword(s):  
Amino Acids ◽  
Experimental Period ◽  
Saline Group ◽  
Group Iii ◽  
Leucine Oxidation ◽  
Group I ◽  
Group Ii ◽  
Plasma Leucine ◽  
Independent Effects

The present study examines the independent effects of amino acids and leucine in modulating insulin's effect on leucine kinetics in 24-h fasted conscious dogs during an experimental period where insulin was infused at 600 mU.kg-1.h-1. Group I (n = 7) received saline, group II (n = 10) received sequential infusions of L-leucine at 0, 1, 3, and 1 mumol.kg-1.min-1 each lasting for 90 min, and group III (n = 6) received L-amino acids with doses of L-leucine matching those of group II. Plasma leucine (mumol/l) was 120 +/- 5 basally and 135 +/- 23 and 129 +/- 12 during the infusion of 3.0 mumol.kg-1.min-1 in groups II and III compared with 40 +/- 3 in group I. Leucine rate of appearance (mumol.kg-1.min-1) was 3.5 +/- 0.3 during the basal period and was suppressed 80% in both groups II and III as compared with 40% in group I (P less than 0.01). Leucine oxidation (basal = 0.7 +/- 0.15 mumol.kg-1.min-1) dropped 20% in group I but increased to threefold basal in group II and twofold in group III (P less than 0.05). Nonoxidative rate of disposal (basal = 2.6 +/- 0.2 mumol.kg-1.min-1) dropped 25% in group I and 55% in group II but did not change in group III. These data show that, in addition to insulin, amino acids and particularly leucine cause a marked suppression of proteolysis. Availability of all amino acids to prevent hypoaminoacidemia is necessary to sustain basal rates of protein synthesis. The infusion of leucine alone resulted in significant stimulation of leucine oxidation.

A New Model for Quantitative In Vivo Microscopic Analysis of Thrombus Formation and Vascular Recanalisation: The Ear of the Hairless (hr/hr) Mouse

1997 ◽  
Vol 78 (05) ◽  
pp. 1408-1414 ◽  
Author(s):  
Frank Roesken ◽  
Martin Ruecker ◽  
Brigitte Vollmar ◽  
Nicole Boeckel ◽  
Eberhard Morgenstern ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Light Exposure ◽  
Thrombus Formation ◽  
Microscopic Analysis ◽  
Cell Interaction ◽  
Vascular Perfusion ◽  
Vessel Occlusion ◽  
Endothelial Cell Interaction ◽  
Platelet Deposition

SummaryThe alteration of rheological blood properties as well as deterioration of vascular perfusion conditions and cell-cell interactions are major determinants of thrombus formation. Herein, we present an experimental model which allows for quantitative in vivo microscopic analysis of these determinants during both thrombus formation and vascular recanalisation. The model does not require surgical preparation procedures, and enables for repeated analysis of identical microvessels over time periods of days or months, respectively. After i.v. administration of FITC-dextran thrombus formation was induced photochemically by light exposure to individual arterioles and venules of the ear of ten anaesthetised hairless mice. In venules, epiillumination induced rapid thrombus formation with first platelet deposition after 0.59 ± 0.04 min and complete vessel occlusion within 7.48 ±1.31 min. After a 24-h time period, 75% of the thrombosed venules were found recanalised. Marked leukocyte-endothelial cell interaction in those venules indicated persistent endothelial cell activation and/or injury, even after an observation period of 7 days. In arterioles, epi-illumination provoked vasomotion, while thrombus formation was significantly (p <0.05) delayed with first platelet deposition after 2.32 ± 0.22 min and complete vessel occlusion within 20.07 ±3.84 min. Strikingly, only one of the investigated arterioles was found recanalised after 24 h, which, however, did not show leukocyte-endothelial cell interaction. Heparin (300 U/kg, i.v.) effectively counteracted the process of thrombus formation in this model, including both first platelet deposition and vessel occlusion. We conclude that the model of the ear of the hairless mouse allows for distinct in vivo analysis of arteriolar and venular thrombus formation/ recanalisation, and, thus, represents an interesting tool for the study of novel antithrombotic and thrombolytic strategies, respectively.

scholarly journals Effect of feeding urea-molasses blocks with incorporated fenbendazole on grazing dairy heifers naturally infected with gastrointestinal nematodes

2003 ◽  
Vol 74 (2) ◽  
Author(s):  
R.M. Waruiru ◽  
C.O. Onyando ◽  
R.O. Machuka
Keyword(s):  
Weight Gain ◽  
Live Weight ◽  
Experimental Period ◽  
Gastrointestinal Nematodes ◽  
Group Iii ◽  
Dairy Heifers ◽  
Helminth Infections ◽  
Group I ◽  
Body Weights ◽  
The Mean

Between June 1999 and August 2000, the effects of feeding medicated urea-molasses supplement blocks on the growth of dairy heifers in a marginal area of central Kenya were assessed by comparing the live-weight gain of supplemented and unsupplemented heifers grazing the same pasture. Thirty-nine heifers with an average age of 9.6 months were initially treated orally with albendazole (10 mg / kg body weight) and assigned to 3 groups : group I was fed urea-molasses blocks with incorporated fenbendazole (MUMB), group II was fed urea-molasses blocks (UMB) and group III heifers (control) received no block supplementation (NBS). Body weights of the heifers and faecal egg counts (FECs) were measured monthly and larval cultures were made of positive faecal samples of each group. The mean cumulative live-weight responses of the MUMB and UMB groups were significantly greater than the NBS group (P < 0.05). However, at the end of the experimental period, the mean weight gain of the MUMB group did not differ from that of the UMB group (P >0.05). The FECs were moderate to low in all groups and decreased progressively with increasing age of the animals; FECs for the urea-molasses-supplemented groups remained significantly lower than those of the NBS group throughout the experimental period (P <0.05). Haemonchus and Trichostrongylus were the predominant nematode genera found in the heifers, but Cooperia, Bunostomum and Oesophagostomum were also present. These results indicate that feeding of urea-molasses blocks substantially reduced production losses attributable to nematode infection of young grazing cattle, and confirms previous observations that well-fed animals are better able to overcome the effects of helminth infections.

scholarly journals Hirudin interruption of heparin-resistant arterial thrombus formation in baboons

Blood ◽  
1991 ◽  
Vol 77 (5) ◽  
pp. 1006-1012 ◽  
Author(s):  
AB Kelly ◽  
UM Marzec ◽  
W Krupski ◽  
A Bass ◽  
Y Cadroy ◽  
...  
Keyword(s):  
Bleeding Time ◽  
Thrombus Formation ◽  
Dependent Manner ◽  
Fibrin Deposition ◽  
Recombinant Hirudin ◽  
Arterial Thrombus ◽  
Dependent Inhibition ◽  
Antithrombotic Effects ◽  
Dose Dependent

Abstract To determine the role of thrombin in high blood flow, platelet- dependent thrombotic and hemostatic processes we measured the relative antithrombotic and antihemostatic effects in baboons of hirudin, a highly potent and specific antithrombin, and compared the effects of heparin, an antithrombin III-dependent inhibitor of thrombin. Thrombus formation was determined in vivo using three relevant models (homologous endarterectomized aorta, collagen-coated tubing, and Dacron vascular graft) by measuring: (1) platelet deposition, using gamma camera imaging of 111In-platelets; (2) fibrin deposition, as assessed by the incorporation of circulating 125I-fibrinogen; and (3) occlusion. The continuous intravenous infusion of 1, 5, and 20 nmol/kg per minute of recombinant hirudin (desulfatohirudin) maintained constant plasma levels of 0.16 +/- 0.03, 0.79 +/- 0.44, and 3.3 +/- 0.77 mumol/mL, respectively. Hirudin interrupted platelet and fibrin deposition in a dose-dependent manner that was profound at the highest dose for all three thrombogenic surfaces and significant at the lowest dose for thrombus formation on endarterectomized aorta. Thrombotic occlusion was prevented by all doses studied. In contrast, heparin did not inhibit either platelet or fibrin deposition when administered at a dose that maximally prolonged clotting times (100 U/kg) (P greater than .1), and only intermediate effects were produced at 10-fold that dose (1,000 U/kg). Moreover, heparin did not prevent occlusion of the test segments. Hirudin inhibited platelet hemostatic function in concert with its antithrombotic effects (bleeding times were prolonged by the intermediate and higher doses). By comparison, intravenous heparin failed to affect the bleeding time at the 100 U/kg dose (P greater than .5), and only minimally prolonged the bleeding time at the 1,000 U/kg dose (P less than .05). We conclude that platelet-dependent thrombotic and hemostatic processes are thrombin-mediated and that the biologic antithrombin hirudin produces a potent, dose-dependent inhibition of arterial thrombus formation that greatly exceeds the minimal antithrombotic effects produced by heparin.

scholarly journals BONE INDUCTION BY BMP-2 EXPRESSING ADENOVIRAL VECTOR IN RATS UNDER TREATMENT WITH FK506

2002 ◽  
Vol 06 (01) ◽  
pp. 23-29 ◽  
Author(s):  
Junya Sonobe ◽  
Kazuhisa Bessho ◽  
Shinji Kaihara ◽  
Yasunori Okubo ◽  
Tadahiko Iizuka
Keyword(s):  
Adenoviral Vector ◽  
Host Immunity ◽  
Bone Morphogenetic Protein 2 ◽  
Control Group ◽  
Group Iii ◽  
Group I ◽  
Morphogenetic Protein ◽  
Human Bone Morphogenetic Protein ◽  
The Right

The purpose of this study was to investigate the effectiveness of human bone morphogenetic protein-2 (BMP-2) expressing adenoviral vector in vivo. The day before vector injection, immunosuppressant FK506 was given subcutaneously to each rat at doses of 12 mg/kg (Group I), 6 mg/kg (Group II) and 3 mg/kg (Group III). FK506 was not administered to the six rats of the control group. Twenty-five liters of AXCAOBMP-2 (3.93 × 109pfu/ml) were injected into the right calf muscle of all rats. On day 21 after vector injection, all groups were investigated radiologically, histologically, and biochemically. Osteoinduction was seen in the AxCAOBMP-2-injected groups with immunosuppression. However, no bone formation was observed in the control group. These findings suggest that AxCAOBMP-2 has the potential of osteoinduction under transient immunosuppression. AxCAOBMP-2 may be useful for future clinical application in bone reconstruction, if host immunity response can be regulated.

scholarly journals Pentoxifylline Attenuates Methionine- and Choline-Deficient-Diet-Induced Steatohepatitis by Suppressing TNF-αExpression and Endoplasmic Reticulum Stress

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Min Kyung Chae ◽  
Sang Gyu Park ◽  
Sun-Ok Song ◽  
Eun Seok Kang ◽  
Bong Soo Cha ◽  
...  
Keyword(s):  
Er Stress ◽  
Deficient Diet ◽  
Group Iii ◽  
Unfolded Protein ◽  
Sd Rats ◽  
Group I ◽  
Hep3b Cells ◽  
Protein Response

Background. Pentoxifylline (PTX) anti-TNF properties are known to exert hepatoprotective effects in various liver injury models. The aim of this study was to investigate whether PTX has beneficial roles in the development of methionine- and choline-deficient-(MCD-) diet-induced NAFLD SD ratsin vivoand TNF-α-induced Hep3B cellsin vitro.Methods. SD Rats were classified according to diet (chow or MCD diet) and treatment (normal saline or PTX injection) over a period of 4 weeks: group I (chow + saline,n=4), group II (chow + PTX), group III (MCD + saline), and group IV (MCD + PTX). Hep3B cells were treated with 100 ng/ml TNF-α(24 h) in the absence or presence of PTX (1 mM).Results. PTX attenuated MCD-diet-induced serum ALT levels and hepatic steatosis. In real-time PCR and western blotting analysis, PTX decreased MCD-diet-induced TNF-alpha mRNA expression and proapoptotic unfolded protein response by ER stress (GRP78, p-eIF2, ATF4, IRE1α, CHOP, and p-JNK activation)in vivo. PTX (1 mM) reduced TNF-α-induced activation of GRP78, p-eIF2, ATF4, IRE1α, and CHOPin vitro.Conclusion. PTX has beneficial roles in the development of MCD-diet-induced steatohepatitis through partial suppression of TNF-αand ER stress.

Immunochemical Studies Of Fibrinogen Products Produced During Thrombosis

1981 ◽  
Author(s):  
R E Canfield
Keyword(s):  
Thrombus Formation ◽  
Factor Xiiia ◽  
Fibrinopeptide A ◽  
Terminal Events ◽  
Α Chain

Immunochemical measurement of the products of fibrinogen proteolysis has provided a method to study the terminal events of coagulation that are initiated by thrombin as well as those events associated with the fibrinolytic actions of plasmin. Thrombin releases fibrinopeptide A (FPA) and later fibrinopeptide B (FPB). Immunologic techniques to measure FPA are now well established; determination of FPB is complicated by degradation of the peptide in plasma. Early plasmin cleavage occurs at the NH2-terminal end of the Bβ-chain of fibrinogen yielding Bβ 1-42. This fragment exhibits limited crossreactivity with antisera to FPB. The action of plasmin at this site on fibrin I may play an important role in determining whether thrombin release of FPA ultimately leads to thrombus formation in vivo. Other early plasmin cleavage products arise from the COOH-terminal half of the α-chain. Details concerning the application of these immunochemical measurements to an understanding of the role of thrombin and plasmin-mediated proteolysis of fibrinogen and fibrin will be discussed. In addition, immunochemical attempts to detect the presence of factor XIIIa-catalyzed crosslinks will also be described.

A New Method for Quantifying Platelet Deposition in Flowing Native Blood in an Ex Vivo Model of Human Thrombogenesis

1998 ◽  
Vol 79 (01) ◽  
pp. 162-168 ◽  
Author(s):  
J. P. Bossavy ◽  
K. S. Sakariassen ◽  
A. Barret ◽  
B. Boneu ◽  
Y. Cadroy
Keyword(s):  
Unfractionated Heparin ◽  
Ex Vivo ◽  
Thrombus Formation ◽  
Plasma Concentrations ◽  
New Method ◽  
Dependent Manner ◽  
Fibrin Deposition ◽  
Simple Method ◽  
Arterial Thrombus ◽  
Platelet Deposition

SummaryNo quantitative, simple and non-radioactive method has been described for measuring the platelet content of experimental thrombi. The aim of the present study was to develop a simple method for quantifying platelets in thrombi formed on thrombogenic surfaces in flowing native human blood. To test the relevance of this new method, the effect of unfractionated heparin on arterial thrombus formation was investigated. Tissue factor (TF)- and collagen-coated coverslips were exposed to non-anticoagulated blood at an arterial wall shear rate (2,600 s–1) for 1 to 4 min. Platelet deposition was quantified by measuring the P-selectin (PS) and β-thromboglobulin (βTG) content of dissolved plasmin-digested thrombi using immunoenzymoassays; fibrin deposition was determined by measuring the D-dimer levels. These results were compared to those established by morphometrical analysis.Morphometric evaluation showed that fibrin deposition was maximum on TF by 1 min perfusion time. Platelets deposited subsequently and reached a maximum at 3 min. On collagen, platelets deposited directly on the collagen fibrils without detectable fibrin deposit. Platelet deposition increased from 1 to 4 min. Platelet deposition quantified by PS was correlated to the values obtained by morphometry (r = 0.72, r = 0.67, p <0.001, on TF and collagen, respectively). As compared to PS, βTG measurements gave an underestimation of the size of the thrombus platelet number. Unfractionated heparin infused through a mixing device proximal to the perfusion chamber to obtain plasma concentrations of 0.5, 1 and 3 IU/ml, reduced fibrin deposition on TF-coated coverslips in a dose-dependent manner (77% reduction at 3 IU/ml, p <0.01), but had no significant effect on platelet deposition (33% at 3 IU/ml, p >0.05). In contrast, heparin had no effect on fibrin or platelet deposition on collagen-coated coverslips.Thus, a new quantitative and simple method for measuring platelet deposition in flowing blood has been developed and characterized. Utilizing this system, we have demonstrated that unfractionated heparin did not inhibit arterial thrombus formation either on procoagulant or on proaggregant surface.

Allograft T Cell Content Influences Early Engraftment after Reduced-Intensity Stem Cell Transplantation (RIST).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3662-3662
Author(s):  
Robert M. Dean ◽  
Daniel H. Fowler ◽  
Nancy M. Hardy ◽  
Jeanne Odom ◽  
Kathleen Castro ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Ex Vivo ◽  
Group Iii ◽  
Donor Chimerism ◽  
Group I ◽  
Gvhd Prophylaxis ◽  
Donor T Cells ◽  
Reduced Intensity

Abstract Allogeneic hematopoietic stem cells (HSC) generally engraft rapidly and completely after myeloablative conditioning. However, with reduced-intensity conditioning (RIC), mixed chimerism and graft failure are more common. Host immune status and HSC number are factors known to affect engraftment after reduced-intensity stem cell transplantation (RIST). In addition, donor T cells within the allograft may also influencethe kinetics of donor engraftment after RIST. To evaluate this, we performed a controlled comparison of engraftment outcomes among 3 groups undergoing RIST, varying by ex vivo T cell depletion (TCD) or in vivo depletion of activated T cells with methotrexate (MTX) to prevent graft-versus-host disease (GVHD). Group I (n = 50) received T cell replete (TCR) peripheral blood stem cells (PBSC) with cyclosporine (CSA) alone for GVHD prophylaxis. Group II (n = 17) received ex vivo TCD PBSC (positive/negative selection with T cell add-back to uniform dose of 1 x 105 CD3+ cells/kg) with CSA alone for GVHD prophylaxis. Group III (n = 31) received TCR PBSC with CSA plus MTX (5 mg/m2 IV x 4 doses) for GVHD prophylaxis. The 3 groups were similarly immunosuppressed from prior therapy before RIST (median absolute lymphocyte counts 330/μL, 260/μL, and 307/μL for Groups I, II, and III, respectively), and received an identical RIC regimen (fludarabine/cyclophosphamide) plus comparable numbers of filgrastim-mobilized PBSC from HLA-matched sibling donors (median 7.9 x 106, 7.6 x 106, and 6.8 x 106 CD34+ cells/kg, respectively; median 3.6 x 108, 1.0 x 105, and 3.2 x 108 CD3+ cells/kg, respectively). Hematopoietic recovery was slowest in Group III, consistent with the myelosuppressive effects of MTX (Table). A greater proportion of patients in Group I achieved complete donor chimerism (≥ 95%) by day +28 than in Groups II or III (P &lt; 0.025), and at day +100, mixed donor chimerism persisted more often in Groups II and III than in Group I patients (P &lt; 0.01). Correspondingly, early (&lt; day +42) occurrence of grade 3–4 acute GVHD, before initiation of planned sequential donor lymphocyte infusions (DLI) in Group II, was more frequent in Group I than in either Groups II or III (p=0.08). Table: Hematopoietic Recovery, Engraftment, and GVHD Group Days to ANC &gt; 500, median (range) Days to plt &gt; 100, median (range) Donor chimerism ≥ 95% Early acute GVHD, grades 3–4 Day +28 Day +100 I 9 (7–13) 15.5 (12-42) 37/44 (84%) 36/38 (95%) 9/50 (18%) II 9 (7–10) 17.5 (11–40) 8/17 (47%) 9/14 (65%) 0/17 (0%) III 14 (7–21) 21.5 (12–85) 23/31 (74%) 21/31 (68%) 2/31 (6%) Thus, the deletion of T cells by either ex vivo TCD or in vivo MTX administration measurably alters the kinetics and degree of donor T cell engraftment after RIST. These observations provide evidence that donor T cells are an independent factor affecting engraftment of allogeneic HSC after RIST by compensating for incomplete host immune ablation. These data also support the hypothesis that a graft-versus-host effect plays a significant role in engraftment after RIST. Manipulation of donor T cells through graft engineering techniques may be a useful strategy to enhance engraftment in the setting of RIST.

Endothelium but Not Platelet-Derived Protein Disulfide Isomerase Is Required for Fibrin Generation during Thrombus Formation in Vivo.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 691-691 ◽  
Author(s):  
Reema Jasuja ◽  
Jaehyung Cho ◽  
Bruce Furie ◽  
Barbara Furie
Keyword(s):  
Endothelial Cells ◽  
Protein Disulfide Isomerase ◽  
Thrombus Formation ◽  
Fibrin Deposition ◽  
Wild Type ◽  
Disulfide Isomerase ◽  
Laser Injury ◽  
Injury Model ◽  
Protein Disulfide

Abstract We have previously reported that protein disulfide isomerase is required in wild-type mice for platelet thrombus formation and fibrin generation in an in vivo laser injury model of thrombosis (Cho et al. J. Clin. Invest., 2008; 118:1123–31). Fibrin deposition after laser injury to the vessel wall in Par4−/− mice, lacking the G protein-coupled platelet thrombin receptor, is independent of platelets or requires minimal platelet activation or accumulation (Vandendries et al. Proc. Natl. Acad. Sci., 2007; 104:288–92). However, protein disulfide isomerase inhibitors have a dramatic effect on fibrin accumulation in Par4− mice, suggesting that these inhibitors may function by a platelet independent mechanism. Here, we compare the contributions of endothelium and platelet-derived protein disulfide isomerase to fibrin generation in the mouse laser injury model of thrombosis. In vitro studies using cultured human umbilical vein endothelial cells and human aortic endothelial cells show that protein disulfide isomerase can be secreted rapidly into the culture medium from these cells upon thrombin stimulation. Using intravital microscopy, we observe that protein disulfide isomerase is not detectable on the vessel wall prior to laser injury but can be detected on the injured cremaster arteriolar wall and in the developing thrombus very rapidly after laser induced injury in the live mouse. The median integrated fluorescence intensity for protein disulfide isomerase in wild-type mice was compared to wild-type mice injected with 10ug/g mouse of Integrilin, an inhibitor of platelet activation and platelet thrombus formation, and thus, an inhibitor of the contribution of platelet derived protein disulfide isomerase to thrombus formation. Protein disulfide isomerase expression was similar in both treated and untreated animals upto 30 seconds post-laser injury. After 30 seconds, the expression of protein disulfide isomerase in integrilin treated mice was significantly decreased compared to that in untreated mice, indicating that the initial protein disulfide isomerase was derived from the endothelium and later additional protein disulfide isomerase was derived from the platelets following their accumulation in the developing thrombus. Fibrin deposition, a measure of thrombin generation was comparable in wild-type mice that had been treated with Integrilin or treated with a control buffer, suggesting that endothelial-derived protein disulfide isomerase was sufficient for fibrin generation. The rate and amount of fibrin generation was indistinguishable in both groups. Furthermore, inhibition of the protein disulfide isomerase with the function blocking monoclonal antibody RL-90 (3ug/g mouse) eliminated any fibrin deposition in wild-type mice that had been treated with Integrilin. Taken together, these data indicate that endothelium-derived protein disulfide isomerase is necessary to support fibrin deposition in vivo in our laser injury model of thrombus formation. The initial protein disulfide isomerase expressed at the site of injury is derived from endothelial cells but platelets activated at the site of thrombus formation contribute, amplify and sustain protein disulfide isomerase expression.

Sign in / Sign up

Export Citation Format

Share Document