Flow Chamber Analyses in Cardiovascular Research: Impact of Platelets and the Intercellular Crosstalk with Endothelial Cells, Leukocytes, and Red Blood Cells

Abstract

Platelets are main drivers of thrombus formation. Besides platelet aggregate formation, platelets interact with different blood cells such as red blood and white blood cells (RBCs, WBCs) and endothelial cells (ECs), to promote thrombus formation and inflammation. In the past, the role of different proteins in platelet adhesion, activation, and aggregate formation has been analyzed using platelets/mice with a genetic loss of a certain protein. These knock-out mouse models have been investigated for changes in experimental arterial thrombosis or hemostasis. In this review, we focused on the Maastricht flow chamber, which is a very elegant tool to analyze thrombus formation under flow using whole blood or different blood cell components of genetically modified mice. Besides, the interaction of platelets with RBCs, WBCs, and ECs under flow conditions has been evaluated with regard to thrombus formation and platelet-mediated inflammation. Importantly, alterations in thrombus formation as emerged in the flow chamber frequently reflect arterial thrombosis in different mouse models. Thus, the results of flow chamber experiments in vitro are excellent indicators for differences in arterial thrombosis in vivo. Taken together, the Maastricht flow chamber can be used to (1) determine the severity of platelet alterations in different knock-out mice; (2) analyze differences in platelet adhesion, aggregation, and activation; (3) investigate collagen and non–collagen-dependent alterations of thrombus formation; and (4) highlight differences in the interaction of platelets with different blood/ECs. Thus, this experimental approach is a useful tool to increase our understanding of signaling mechanisms that drive arterial thrombosis and hemostasis.

To Gain Insights into the Pathophysiological Mechanisms of the Thrombo-Inflammatory Process in the Atherosclerotic Plaque

“…In thromboinflammation, platelets play an important role ( Figure 1 ) [ 7 , 8 , 9 ]. Upon activation, they create heterotypic activation complexes with monocytes and neutrophils by binding to the adhesion molecule P-selectin (CD62P).…”

“…Recent studies show that deep vein thrombosis formation is not only related to platelets and red blood cells, but also involves monocytes and neutrophils [ 168 , 169 , 170 ]. Researchers have been aware of the role of platelets and platelet-derived factors in inflammation since the beginning with ongoing research supporting their impact [ 2 , 3 , 7 , 32 , 102 ]. The traditional cellular players of inflammation and thrombosis fully intertwine, validating the term thromboinflammation.…”

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“…The review article by Kim Jürgen Krott et al 2 highlights how the process of arterial thrombosis can be studied mechanistically using flow chamber models. The authors put focus on the Maastricht flow chamber and explain how this model can complement in vivo mouse thrombosis models.…”