10.3389/fcvm.2019.00099.s001
Magdolna Nagy
Magdolna
Nagy
Johanna P. van Geffen
Johanna P.
van Geffen
David Stegner
David
Stegner
David J. Adams
David J.
Adams
Attila Braun
Attila
Braun
Susanne M. de Witt
Susanne M.
de Witt
Margitta Elvers
Margitta
Elvers
Mitchell J. Geer
Mitchell J.
Geer
Marijke J. E. Kuijpers
Marijke J. E.
Kuijpers
Karl Kunzelmann
Karl
Kunzelmann
Jun Mori
Jun
Mori
Cécile Oury
Cécile
Oury
Joachim Pircher
Joachim
Pircher
Irina Pleines
Irina
Pleines
Alastair W. Poole
Alastair W.
Poole
Yotis A. Senis
Yotis A.
Senis
Remco Verdoold
Remco
Verdoold
Christian Weber
Christian
Weber
Bernhard Nieswandt
Bernhard
Nieswandt
Johan W. M. Heemskerk
Johan W. M.
Heemskerk
Constance C. F. M. J. Baaten
Constance C. F. M. J.
Baaten
Data_Sheet_1_Comparative Analysis of Microfluidics Thrombus Formation in Multiple Genetically Modified Mice: Link to Thrombosis and Hemostasis.PDF
Frontiers
2019
arterial thrombus formation
bleeding
collagen
glycoprotein VI
platelets
microfluidics
2019-07-30 04:18:03
Dataset
https://frontiersin.figshare.com/articles/dataset/Data_Sheet_1_Comparative_Analysis_of_Microfluidics_Thrombus_Formation_in_Multiple_Genetically_Modified_Mice_Link_to_Thrombosis_and_Hemostasis_PDF/9162893
<p>Genetically modified mice are indispensable for establishing the roles of platelets in arterial thrombosis and hemostasis. Microfluidics assays using anticoagulated whole blood are commonly used as integrative proxy tests for platelet function in mice. In the present study, we quantified the changes in collagen-dependent thrombus formation for 38 different strains of (genetically) modified mice, all measured with the same microfluidics chamber. The mice included were deficient in platelet receptors, protein kinases or phosphatases, small GTPases or other signaling or scaffold proteins. By standardized re-analysis of high-resolution microscopic images, detailed information was obtained on altered platelet adhesion, aggregation and/or activation. For a subset of 11 mouse strains, these platelet functions were further evaluated in rhodocytin- and laminin-dependent thrombus formation, thus allowing a comparison of glycoprotein VI (GPVI), C-type lectin-like receptor 2 (CLEC2) and integrin α<sub>6</sub>β<sub>1</sub> pathways. High homogeneity was found between wild-type mice datasets concerning adhesion and aggregation parameters. Quantitative comparison for the 38 modified mouse strains resulted in a matrix visualizing the impact of the respective (genetic) deficiency on thrombus formation with detailed insight into the type and extent of altered thrombus signatures. Network analysis revealed strong clusters of genes involved in GPVI signaling and Ca<sup>2+</sup> homeostasis. The majority of mice demonstrating an antithrombotic phenotype in vivo displayed with a larger or smaller reduction in multi-parameter analysis of collagen-dependent thrombus formation in vitro. Remarkably, in only approximately half of the mouse strains that displayed reduced arterial thrombosis in vivo, this was accompanied by impaired hemostasis. This was also reflected by comparing in vitro thrombus formation (by microfluidics) with alterations in in vivo bleeding time. In conclusion, the presently developed multi-parameter analysis of thrombus formation using microfluidics can be used to: (i) determine the severity of platelet abnormalities; (ii) distinguish between altered platelet adhesion, aggregation and activation; and (iii) elucidate both collagen and non-collagen dependent alterations of thrombus formation. This approach may thereby aid in the better understanding and better assessment of genetic variation that affect in vivo arterial thrombosis and hemostasis.</p>