In vivo modeling of docosahexaenoic acid and eicosapentaenoic acid-mediated inhibition of both platelet function and accumulation in arterial thrombi

Reheman Adili, Ellen M. Voigt, Jordan L. Bormann, Kaitlynn N. Foss, Luke J. Hurley, Evan S. Meyer, Amber J. Veldman, Katherine A. Mast, Joshua L. West, Sidney W. Whiteheart, Michael Holinstat, Mark K. Larson

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)271-279
Number of pages9
JournalPlatelets
Volume30
Issue number2
DOIs
StatePublished - Feb 17 2019

Bibliographical note

Funding Information:
This work was supported in part by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health [grant number P20GM103443 to ML, LH, and EM]; the National Institutes of Health Office of Dietary Supplement [grant number GM105671 to MH], [grant number HL114405 to MH] as well as funding from the National Science Foundation/EPSCoR program [grant number IIA-1355423]; the state of South Dakota (to ML, EV, KF, AV); and an undergraduate fellowship from the American Physiological Society (to JB). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the National Science Foundation.

Publisher Copyright:
© 2017, © 2017 Taylor & Francis.

Keywords

  • Intravital microscopy
  • omega-3 fatty acids
  • platelet activation
  • platelets
  • thrombosis

ASJC Scopus subject areas

  • Hematology

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