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In vivo modeling of docosahexaenoic acid and eicosapentaenoic acid-mediated inhibition of both platelet function and accumulation in arterial thrombi.
Adili, Reheman; Voigt, Ellen M; Bormann, Jordan L; Foss, Kaitlynn N; Hurley, Luke J; Meyer, Evan S; Veldman, Amber J; Mast, Katherine A; West, Joshua L; Whiteheart, Sidney W; Holinstat, Michael; Larson, Mark K.
Afiliación
  • Adili R; a Department of Pharmacology , University of Michigan , Ann Arbor , MI , USA.
  • Voigt EM; b Department of Biology , Augustana University , Sioux Falls , SD , USA.
  • Bormann JL; b Department of Biology , Augustana University , Sioux Falls , SD , USA.
  • Foss KN; b Department of Biology , Augustana University , Sioux Falls , SD , USA.
  • Hurley LJ; b Department of Biology , Augustana University , Sioux Falls , SD , USA.
  • Meyer ES; b Department of Biology , Augustana University , Sioux Falls , SD , USA.
  • Veldman AJ; b Department of Biology , Augustana University , Sioux Falls , SD , USA.
  • Mast KA; a Department of Pharmacology , University of Michigan , Ann Arbor , MI , USA.
  • West JL; a Department of Pharmacology , University of Michigan , Ann Arbor , MI , USA.
  • Whiteheart SW; c Department of Molecular and Cellular Biochemistry , University of Kentucky , Lexington , KY , USA.
  • Holinstat M; a Department of Pharmacology , University of Michigan , Ann Arbor , MI , USA.
  • Larson MK; b Department of Biology , Augustana University , Sioux Falls , SD , USA.
Platelets ; 30(2): 271-279, 2019.
Article en En | MEDLINE | ID: mdl-29286871
Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are associated with a variety of cellular alterations that mitigate cardiovascular disease. However, pinpointing the positive therapeutic effects is challenging due to inconsistent clinical trial results and overly simplistic in vitro studies. Here we aimed to develop realistic models of n-3 PUFA effects on platelet function so that preclinical results can better align with and predict clinical outcomes. Human platelets incubated with the n-3 PUFAs docosahexaenoic acid and eicosapentaenoic acid were stimulated with agonist combinations mirroring distinct regions of a growing thrombus. Platelet responses were then monitored in a number of ex-vivo functional assays. Furthermore, intravital microscopy was used to monitor arterial thrombosis and fibrin deposition in mice fed an n-3 PUFA-enriched diet. We found that n-3 PUFA treatment had minimal effects on many basic ex-vivo measures of platelet function using agonist combinations. However, n-3 PUFA treatment delayed platelet-derived thrombin generation in both humans and mice. This impaired thrombin production paralleled a reduced platelet accumulation within thrombi formed in either small arterioles or larger arteries of mice fed an n-3 PUFA-enriched diet, without impacting P-selectin exposure. Despite an apparent lack of robust effects in many ex-vivo assays of platelet function, increased exposure to n-3 PUFAs reduces platelet-mediated thrombin generation and attenuates elements of thrombus formation. These data support the cardioprotective value of-3 PUFAs and strongly suggest that they modify elements of platelet function in vivo.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Plaquetas / Ácidos Grasos Omega-3 / Ácido Eicosapentaenoico / Ácidos Docosahexaenoicos Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Platelets Asunto de la revista: HEMATOLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Plaquetas / Ácidos Grasos Omega-3 / Ácido Eicosapentaenoico / Ácidos Docosahexaenoicos Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Platelets Asunto de la revista: HEMATOLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido