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Paul F Mcdonagh - One of the best experts on this subject based on the ideXlab platform.

  • Platelet Microparticle formation is increased in mice with diet induced diabetes
    The FASEB Journal, 2006
    Co-Authors: Melissa Maes, Lisa Davidson, Paul F Mcdonagh, Leslie S Ritter
    Abstract:

    Type 2 diabetes is associated with increased Platelet Microparticle (PMP) formation and Platelet P-selectin expression which contribute to a prothrombotic state. The purpose of this study was to determine if PMP formation and P-selectin expression were increased in the high-fat diet induced mouse model of diabetes (DID). C57BL6/J male mice, age 4 weeks, were randomized to standard or 60% beef lard chow for 4 months. One mL of sodium citrated blood was withdrawn from isofluorane anesthetized mice (N=5/group). Samples were incubated with PBS or A23187 for 10 minutes. Samples were then incubated with PE-conjugated anti-mouse CD61, FITC-conjugated anti-mouse CD62P or isotype control, fixed with 1% paraformaldehyde, and placed on ice until flow cytometry acquisition and analysis. After 4 months of diet all DID mice were obese (34.7±0.9 v.50.0±1.2 gm) and hyperglycemic (181.0±13.1 v. 235.2±10.4 mg/dl). We found that PMP formation was elevated in the DID mice compared to control (2569±324 v. 4802±791/10000 plate...

  • thrombin activity and Platelet Microparticle formation are increased in type 2 diabetic Platelets a potential correlation with caspase activation
    Thrombosis Research, 2002
    Co-Authors: Zoe Cohen, Raoul Gonzales, Grace Davisgorman, Jack G Copeland, Paul F Mcdonagh
    Abstract:

    Diabetics suffer from many complications including a prothrombotic condition. Activated Platelet membrane provides an anchor, phosphatidylserine, for the attachment of the prothrombinase complex, which allows increased thrombin formation. This study aimed to further elucidate the interrelationship between coagulation proteins and activated Platelets in type 2 diabetic blood. We found that there was a significant increase (30×) in thrombin activity in the type 2 diabetic (ZDF) blood as compared to age-matched (ZL) controls (p<0.001). There was also a significant increase in the number of Platelet Microparticles in the type 2 diabetic rat compared to the lean control (p<0.001). Further, there were significant increases in caspase-3, -6, and -8 activities in the type 2 diabetic rats as compared to the lean controls (p<0.05). The combination of increased thrombin activity, increased PMP formation and increased caspase activity may contribute to the hypercoagulability of the diabetic blood. These results give more insight into the mechanisms underlying the interrelationship between diabetic Platelets and coagulation proteins causing a prothrombotic condition in this patient population at increased risk from thromboembolic events.

  • brief communication thrombin activity and Platelet Microparticle formation are increased in type 2 diabetic Platelets a potential correlation with caspase activation
    2002
    Co-Authors: Raoul Gonzales, Grace Davisgorman, Jack G Copeland, Paul F Mcdonagh
    Abstract:

    Diabetics suffer from many complications including a prothrombotic condition. Activated Platelet membrane provides an anchor, phosphatidylserine, for the attachment of the prothrombinase complex, which allows increased thrombin formation. This study aimed to further elucidate the interrelationship between coagulation proteins and activated Platelets in type 2 diabetic blood. We found that there was a significant increase (30) in thrombin activity in the type 2 diabetic (ZDF) blood as compared to age-matched (ZL) controls (p<0.001). There was also a significant increase in the number of Platelet Microparticles in the type 2 diabetic rat compared to the lean control (p<0.001). Further, there were significant increases in caspase-3, -6, and -8 activities in the type 2 diabetic rats as compared to the lean controls (p<0.05). The combination of increased thrombin activity, increased PMP formation and increased caspase activity may contribute to the hypercoagulability of the diabetic blood. These results give more insight into the mechanisms underlying the interrelationship between diabetic Platelets and coagulation proteins causing a prothrombotic condition in this patient population at increased risk from thromboembolic events. D 2002 Elsevier Science Ltd. All rights reserved.

Kjell S Sakariassen - One of the best experts on this subject based on the ideXlab platform.

  • shear induced Platelet activation and Platelet Microparticle formation in native human blood
    Thrombosis Research, 1998
    Co-Authors: Kjell S Sakariassen, Pl A Holme, Una Orvim, Marius R Barstad, Nils Olav Solum, Frank Brosstad
    Abstract:

    Abstract Shear-induced Platelet activation and Platelet Microparticle formation are triggered in native human blood by high arterial shear or by a sudden increase in shear as introduced by a stenosis with potential consequences for collagen-induced Platelet thrombus formation. Blood was drawn from healthy volunteers and directly perfused ex vivo over various well-defined eccentric stenoses. Shear-induced Platelet activation was determined by using flow cytometry to assess: 1) GPIIb-IIIa activation by fluorescein isothiocyanate (FITC)-labeled Mab PAC-1; and 2) translocation of membrane aminophospholipids (procoagulant activity) by FITC-labeled Annexin V. Microparticle formation was measured by flow cytometry and FITC-labeled Mab Y2/51 directed against GPIIIa. Significant Platelet activation and Platelet Microparticle formation were elicited when the wall shear rate reached 10,500 sec −1 for a period of 0.075 sec. Prolonged exposure to or a rapid increase in shear further enhanced activation and Microparticle formation. Shear-induced Platelet activation was associated with significantly increased collagen-induced Platelet thrombus formation that was insensitive to aspirin ingestion. Exposure of native blood to very high shear thus activates Platelets to express GPIIb-IIIa, renders the Platelet membrane procoagulant and stimulates Microparticle formation. These responses are associated with enhanced collagen-induced thrombus formation by prostaglandin-independent mechanisms.

  • shear induced Platelet activation and Platelet Microparticle formation at blood flow conditions as in arteries with a severe stenosis
    Arteriosclerosis Thrombosis and Vascular Biology, 1997
    Co-Authors: Pl A Holme, Una Orvim, Marius R Barstad, Nils Olav Solum, Frank Brosstad, Maria J A G Hamers, Kjell S Sakariassen
    Abstract:

    Abstract In the present study, we investigated whether high arterial shear stresses at various exposure times or a sudden increase in shear stress introduced by a stenosis affect Platelet activation and Platelet Microparticle formation in native human blood. We used a parallel-plate perfusion chamber device through which nonanticoagulated human blood was drawn (10 mL/min) by a pump directly from an antecubital vein through the flow channel of a perfusion chamber at wall shear rates of 420, 2600, and 10 500 s−1. In another set of experiments, an eccentric stenosis was introduced into the flow channel. Wall shear rates of 2600 or 10 500 s−1 at the stenosis apex were maintained at the same flow rate. The wall shear rate upstream and downstream of these stenoses was 420 s−1. A shear rate of 420 s−1 is within the range of those encountered in healthy small coronary arteries, whereas those of 2600 and 10 500 s−1 are representative for vessels with various degrees of stenotic lesions. The blood was exposed to these shear rates for periods varying from 0.075 to 3.045 seconds. Platelet activation was assessed as activated glycoprotein (GP) IIb/IIIa by FITC-labeled monoclonal antibody (MAb) PAC-1 and aminophospholipid translocation by FITC-labeled annexin V. Microparticle formation was quantified by FITC-labeled MAb Y2/51 directed against GP IIIa. Significant Platelet activation and formation of Microparticles were observed at 10 500 s−1 only ( P <.008). This shear-induced Platelet activation and Microparticle formation were enhanced by introduction of a thrombus-promoting surface consisting of type III human collagen fibrils. Introduction of the most severe stenosis at 10 500 s−1 further increased Platelet activation ( P <.017). The collagen-induced thrombus formation increased the Platelet thrombus volume at 10 500 s−1 from 16.5 to 33.8 μm3/μm2 ( P <.003) on the stenosis apex when the most severe stenosis was used. A correlation ( P <.0001) between Platelet thrombus volume and Platelet Microparticle formation was observed in the presence of the eccentric stenoses. Apparently, high shear stress (315 dynes/cm2 at 10 500 s−1), as encountered in severe atherosclerotic arteries, activated Platelets and triggered Platelet Microparticle formation. In contrast, no significant Platelet activation or formation of Platelet Microparticles was observed at physiological shear (420 s−1) or at the shear condition simulating shear in arteries with a less severe stenosis (2600 s−1). The data imply that Platelets are activated and form Microparticles in native blood at very high shear stresses. These events are potentiated by prolonged exposure to the high shear or by a sudden change of increasing shear due to the stenosis. The latter situation apparently enhances Platelet thrombus formation at the stenosis.

Marjam Karlsson Ott - One of the best experts on this subject based on the ideXlab platform.

  • Procoagulant Behavior and Platelet Microparticle Generation
    2016
    Co-Authors: On Nanoporous Alumina, Natalia Ferraz, Jaan Hong, Marjam Karlsson Ott
    Abstract:

    ABSTRACT: In the present work, we have investigated Platelet Microparticle (PMP) generation in whole blood after contact with nanoporous alumina. Alumina membranes with pore sizes of 20 and 200 nm in diameter were incubated with whole blood and the number of PMP in the fluid phase was determined by flow cytometry. The role of the complement system in PMP generation was investigated using an analog of the potent complement inhibitor compstatin. Moreover, the procoagulant activity of the two pore size membranes were compared by measuring thrombin formation. Results indicated that PMP were not present in the fluid phase after whole blood contact with either of the alumina membranes. However, scanning electron microscope micrographs clearly showed the presence of PMP clusters on the 200 nm pore size alumina, while PMP were practically absent on the 20nm membrane. We probed no influence of complement activation in PMP generation and adhesion and we hypothesize that other specific material-related protein–Platelet interactions are taking place. A clear difference in procoagulant activity between the membranes could also be seen, 20 nm alumina showed 100 % higher procoagulant activity than 200nm membrane. By combining surface evaluation and flow cytometry *Author to whom correspondence should be addressed

  • procoagulant behavior and Platelet Microparticle generation on nanoporous alumina
    Journal of Biomaterials Applications, 2010
    Co-Authors: Natalia Ferraz, Jaan Hong, Marjam Karlsson Ott
    Abstract:

    In the present work, we have investigated Platelet Microparticle (PMP) generation in whole blood after contact with nanoporous alumina. Alumina membranes with pore sizes of 20 and 200 nm in diameter were incubated with whole blood and the number of PMP in the fluid phase was determined by flow cytometry. The role of the complement system in PMP generation was investigated using an analog of the potent complement inhibitor compstatin. Moreover, the procoagulant activity of the two pore size membranes were compared by measuring thrombin formation. Results indicated that PMP were not present in the fluid phase after whole blood contact with either of the alumina membranes. However, scanning electron microscope micrographs clearly showed the presence of PMP clusters on the 200 nm pore size alumina, while PMP were practically absent on the 20 nm membrane. We probed no influence of complement activation in PMP generation and adhesion and we hypothesize that other specific material-related protein—Platelet inter...

  • Influence of nanoporesize on Platelet adhesion and activation
    Journal of Materials Science: Materials in Medicine, 2008
    Co-Authors: Natalia Ferraz, Jaan Hong, Jan Carlsson, Marjam Karlsson Ott
    Abstract:

    In this study we have evaluated the influence of biomaterial nano-topography on Platelet adhesion and activation. Nano-porous alumina membranes with pore diameters of 20 and 200 nm were incubated with whole blood and Platelet rich plasma. Platelet number, adhesion and activation were determined by using a coulter hematology analyzer, scanning electron microscopy, immunocytochemical staining in combination with light microscopy and by enzyme immunoassay. Special attention was paid to cell morphology, Microparticle generation, P-selectin expression and β-TG production. Very few Platelets were found on the 200 nm alumina as compared to the 20 nm membrane. The Platelets found on the 20 nm membrane showed signs of activation such as spread morphology and protruding filipodia as well as P-selectin expression. However no Microparticles were detected on this surface. Despite the fact that very few Platelets were found on the 200 nm alumina in contrast to the 20 nm membrane many Microparticles were detected on this surface. Interestingly, all Microparticles were found inside circular shaped areas of approximately 3 μm in diameter. Since this is the approximate size of a Platelet we speculate that this is evidence of transient, non-adherent Platelet contact with the surface, which has triggered Platelet Microparticle generation. To the authors knowledge, this is the first study that demonstrates how nanotexture can influence Platelet Microparticle generation. The study highlights the importance of understanding molecular and cellular events on nano-level when designing new biomaterials.

Weiyi Feng - One of the best experts on this subject based on the ideXlab platform.

  • β 3 phosphorylation of Platelet α iib β 3 is crucial for stability of arterial thrombus and Microparticle formation in vivo
    Thrombosis Journal, 2017
    Co-Authors: Weiyi Feng, Manojkumar Valiyaveettil, Tejasvi Dudiki, Ganapati H Mahabeleshwar, Patrick Andre, Eugene A Podrez, Tatiana V Byzova
    Abstract:

    It is well accepted that functional activity of Platelet integrin αIIbβ3 is crucial for hemostasis and thrombosis. The β3 subunit of the complex undergoes tyrosine phosphorylation shown to be critical for outside-in integrin signaling and Platelet clot retraction ex vivo. However, the role of this important signaling event in other aspects of prothrombotic Platelet function is unknown. Here, we assess the role of β3 tyrosine phosphorylation in Platelet function regulation with a knock-in mouse strain, where two β3 cytoplasmic tyrosines are mutated to phenylalanine (DiYF). We employed Platelet transfusion technique and intravital microscopy for observing the cellular events involved in specific steps of thrombus growth to investigate in detail the role of β3 tyrosine phosphorylation in arterial thrombosis in vivo. Upon injury, DiYF mice exhibited delayed arterial occlusion and unstable thrombus formation. The mean thrombus volume in DiYF mice formed on collagen was only 50% of that in WT. This effect was attributed to DiYF Platelets but not to other blood cells and endothelium, which also carry these mutations. Transfusion of isolated DiYF but not WT Platelets into irradiated WT mice resulted in reversal of the thrombotic phenotype and significantly prolonged blood vessel occlusion times. DiYF Platelets exhibited reduced adhesion to collagen under in vitro shear conditions compared to WT Platelets. Decreased Platelet Microparticle release after activation, both in vitro and in vivo, were observed in DiYF mice compared to WT mice. β3 tyrosine phosphorylation of Platelet αIIbβ3 regulates both Platelet pro-thrombotic activity and the formation of a stable Platelet thrombus, as well as arterial Microparticle release.

  • β3 phosphorylation of Platelet αIIbβ3 is crucial for stability of arterial thrombus and Microparticle formation in vivo
    'Springer Science and Business Media LLC', 2017
    Co-Authors: Weiyi Feng, Manojkumar Valiyaveettil, Tejasvi Dudiki, Ganapati H Mahabeleshwar, Patrick Andre, Eugene A Podrez, Tatiana V Byzova
    Abstract:

    Abstract Background It is well accepted that functional activity of Platelet integrin αIIbβ3 is crucial for hemostasis and thrombosis. The β3 subunit of the complex undergoes tyrosine phosphorylation shown to be critical for outside-in integrin signaling and Platelet clot retraction ex vivo. However, the role of this important signaling event in other aspects of prothrombotic Platelet function is unknown. Method Here, we assess the role of β3 tyrosine phosphorylation in Platelet function regulation with a knock-in mouse strain, where two β3 cytoplasmic tyrosines are mutated to phenylalanine (DiYF). We employed Platelet transfusion technique and intravital microscopy for observing the cellular events involved in specific steps of thrombus growth to investigate in detail the role of β3 tyrosine phosphorylation in arterial thrombosis in vivo. Results Upon injury, DiYF mice exhibited delayed arterial occlusion and unstable thrombus formation. The mean thrombus volume in DiYF mice formed on collagen was only 50% of that in WT. This effect was attributed to DiYF Platelets but not to other blood cells and endothelium, which also carry these mutations. Transfusion of isolated DiYF but not WT Platelets into irradiated WT mice resulted in reversal of the thrombotic phenotype and significantly prolonged blood vessel occlusion times. DiYF Platelets exhibited reduced adhesion to collagen under in vitro shear conditions compared to WT Platelets. Decreased Platelet Microparticle release after activation, both in vitro and in vivo, were observed in DiYF mice compared to WT mice. Conclusion β3 tyrosine phosphorylation of Platelet αIIbβ3 regulates both Platelet pro-thrombotic activity and the formation of a stable Platelet thrombus, as well as arterial Microparticle release

Tatiana V Byzova - One of the best experts on this subject based on the ideXlab platform.

  • β 3 phosphorylation of Platelet α iib β 3 is crucial for stability of arterial thrombus and Microparticle formation in vivo
    Thrombosis Journal, 2017
    Co-Authors: Weiyi Feng, Manojkumar Valiyaveettil, Tejasvi Dudiki, Ganapati H Mahabeleshwar, Patrick Andre, Eugene A Podrez, Tatiana V Byzova
    Abstract:

    It is well accepted that functional activity of Platelet integrin αIIbβ3 is crucial for hemostasis and thrombosis. The β3 subunit of the complex undergoes tyrosine phosphorylation shown to be critical for outside-in integrin signaling and Platelet clot retraction ex vivo. However, the role of this important signaling event in other aspects of prothrombotic Platelet function is unknown. Here, we assess the role of β3 tyrosine phosphorylation in Platelet function regulation with a knock-in mouse strain, where two β3 cytoplasmic tyrosines are mutated to phenylalanine (DiYF). We employed Platelet transfusion technique and intravital microscopy for observing the cellular events involved in specific steps of thrombus growth to investigate in detail the role of β3 tyrosine phosphorylation in arterial thrombosis in vivo. Upon injury, DiYF mice exhibited delayed arterial occlusion and unstable thrombus formation. The mean thrombus volume in DiYF mice formed on collagen was only 50% of that in WT. This effect was attributed to DiYF Platelets but not to other blood cells and endothelium, which also carry these mutations. Transfusion of isolated DiYF but not WT Platelets into irradiated WT mice resulted in reversal of the thrombotic phenotype and significantly prolonged blood vessel occlusion times. DiYF Platelets exhibited reduced adhesion to collagen under in vitro shear conditions compared to WT Platelets. Decreased Platelet Microparticle release after activation, both in vitro and in vivo, were observed in DiYF mice compared to WT mice. β3 tyrosine phosphorylation of Platelet αIIbβ3 regulates both Platelet pro-thrombotic activity and the formation of a stable Platelet thrombus, as well as arterial Microparticle release.

  • β3 phosphorylation of Platelet αIIbβ3 is crucial for stability of arterial thrombus and Microparticle formation in vivo
    'Springer Science and Business Media LLC', 2017
    Co-Authors: Weiyi Feng, Manojkumar Valiyaveettil, Tejasvi Dudiki, Ganapati H Mahabeleshwar, Patrick Andre, Eugene A Podrez, Tatiana V Byzova
    Abstract:

    Abstract Background It is well accepted that functional activity of Platelet integrin αIIbβ3 is crucial for hemostasis and thrombosis. The β3 subunit of the complex undergoes tyrosine phosphorylation shown to be critical for outside-in integrin signaling and Platelet clot retraction ex vivo. However, the role of this important signaling event in other aspects of prothrombotic Platelet function is unknown. Method Here, we assess the role of β3 tyrosine phosphorylation in Platelet function regulation with a knock-in mouse strain, where two β3 cytoplasmic tyrosines are mutated to phenylalanine (DiYF). We employed Platelet transfusion technique and intravital microscopy for observing the cellular events involved in specific steps of thrombus growth to investigate in detail the role of β3 tyrosine phosphorylation in arterial thrombosis in vivo. Results Upon injury, DiYF mice exhibited delayed arterial occlusion and unstable thrombus formation. The mean thrombus volume in DiYF mice formed on collagen was only 50% of that in WT. This effect was attributed to DiYF Platelets but not to other blood cells and endothelium, which also carry these mutations. Transfusion of isolated DiYF but not WT Platelets into irradiated WT mice resulted in reversal of the thrombotic phenotype and significantly prolonged blood vessel occlusion times. DiYF Platelets exhibited reduced adhesion to collagen under in vitro shear conditions compared to WT Platelets. Decreased Platelet Microparticle release after activation, both in vitro and in vivo, were observed in DiYF mice compared to WT mice. Conclusion β3 tyrosine phosphorylation of Platelet αIIbβ3 regulates both Platelet pro-thrombotic activity and the formation of a stable Platelet thrombus, as well as arterial Microparticle release