Rational design of an ex vivo model of thrombosis

Michelle A. Berny; Ishan A. Patel; Tara C. White-Adams; Patrick Simonson; Andrá S. Gruber; Sandra Rugonyi; Owen J.T. McCarty

doi:10.1007/s12195-010-0103-5

Rational design of an ex vivo model of thrombosis

Michelle A. Berny, Ishan A. Patel, Tara C. White-Adams, Patrick Simonson, Andrá S. Gruber, Sandra Rugonyi, Owen J.T. McCarty

Biomedical Engineering

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

The underlying pathogenesis of cardiovascular disease is the formation of occlusive thrombi. While many well-defined animal models recapitulate the process of intravascular thrombosis, there is a need for validated ex vivo models of occlusive thrombus formation. Using the force of gravity to provide a constant pressure gradient, we designed and validated an ex vivo model of thrombosis. Times to occlusion on a collagen matrix in our model were within the range of occlusion times observed in murine thrombosis models. Prolongation of time to occlusion in the presence of platelet α_IIbβ ₃ antagonists or inhibitors to thrombin or activated factor X is in agreement with established mechanisms of thrombus formation. The use of this model may be expanded to characterize the mechanisms of thrombosis and to determine the efficacy of pharmacological agents designed to prevent occlusive thrombus formation.

Original language	English (US)
Pages (from-to)	187-189
Number of pages	3
Journal	Cellular and Molecular Bioengineering
Volume	3
Issue number	2
DOIs	https://doi.org/10.1007/s12195-010-0103-5
State	Published - Jun 2010

Keywords

Coagulation
Platelets
Shear
Thrombosis model

ASJC Scopus subject areas

Modeling and Simulation
General Biochemistry, Genetics and Molecular Biology

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10.1007/s12195-010-0103-5

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title = "Rational design of an ex vivo model of thrombosis",

abstract = "The underlying pathogenesis of cardiovascular disease is the formation of occlusive thrombi. While many well-defined animal models recapitulate the process of intravascular thrombosis, there is a need for validated ex vivo models of occlusive thrombus formation. Using the force of gravity to provide a constant pressure gradient, we designed and validated an ex vivo model of thrombosis. Times to occlusion on a collagen matrix in our model were within the range of occlusion times observed in murine thrombosis models. Prolongation of time to occlusion in the presence of platelet αIIbβ 3 antagonists or inhibitors to thrombin or activated factor X is in agreement with established mechanisms of thrombus formation. The use of this model may be expanded to characterize the mechanisms of thrombosis and to determine the efficacy of pharmacological agents designed to prevent occlusive thrombus formation.",

keywords = "Coagulation, Platelets, Shear, Thrombosis model",

author = "Berny, {Michelle A.} and Patel, {Ishan A.} and White-Adams, {Tara C.} and Patrick Simonson and Gruber, {Andr{\'a} S.} and Sandra Rugonyi and McCarty, {Owen J.T.}",

note = "Funding Information: Supported by American Heart Association Grants 09PRE2230117 (M.A.B.), 0910025G (T.C.W.), and 09GRNT2150003 (O.J.T.M.). M.A.B. and T.C.W. are ARCS scholars; T.C.W. is a Vertex Scholar; I.A.P. is the recipient of a Johnson scholarship.",

year = "2010",

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doi = "10.1007/s12195-010-0103-5",

language = "English (US)",

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journal = "Cellular and Molecular Bioengineering",

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AU - Berny, Michelle A.

AU - Patel, Ishan A.

AU - White-Adams, Tara C.

AU - Simonson, Patrick

AU - Gruber, Andrá S.

AU - Rugonyi, Sandra

AU - McCarty, Owen J.T.

N1 - Funding Information: Supported by American Heart Association Grants 09PRE2230117 (M.A.B.), 0910025G (T.C.W.), and 09GRNT2150003 (O.J.T.M.). M.A.B. and T.C.W. are ARCS scholars; T.C.W. is a Vertex Scholar; I.A.P. is the recipient of a Johnson scholarship.

PY - 2010/6

Y1 - 2010/6

N2 - The underlying pathogenesis of cardiovascular disease is the formation of occlusive thrombi. While many well-defined animal models recapitulate the process of intravascular thrombosis, there is a need for validated ex vivo models of occlusive thrombus formation. Using the force of gravity to provide a constant pressure gradient, we designed and validated an ex vivo model of thrombosis. Times to occlusion on a collagen matrix in our model were within the range of occlusion times observed in murine thrombosis models. Prolongation of time to occlusion in the presence of platelet αIIbβ 3 antagonists or inhibitors to thrombin or activated factor X is in agreement with established mechanisms of thrombus formation. The use of this model may be expanded to characterize the mechanisms of thrombosis and to determine the efficacy of pharmacological agents designed to prevent occlusive thrombus formation.

AB - The underlying pathogenesis of cardiovascular disease is the formation of occlusive thrombi. While many well-defined animal models recapitulate the process of intravascular thrombosis, there is a need for validated ex vivo models of occlusive thrombus formation. Using the force of gravity to provide a constant pressure gradient, we designed and validated an ex vivo model of thrombosis. Times to occlusion on a collagen matrix in our model were within the range of occlusion times observed in murine thrombosis models. Prolongation of time to occlusion in the presence of platelet αIIbβ 3 antagonists or inhibitors to thrombin or activated factor X is in agreement with established mechanisms of thrombus formation. The use of this model may be expanded to characterize the mechanisms of thrombosis and to determine the efficacy of pharmacological agents designed to prevent occlusive thrombus formation.

KW - Coagulation

KW - Platelets

KW - Shear

KW - Thrombosis model

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ER -

Rational design of an ex vivo model of thrombosis

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Keywords

ASJC Scopus subject areas

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