Article

Dysfunctional platelet membrane receptors: from humans to mice

The Room Research Center for Arteriosclerosis and Thrombosis, Division of Experimental Hemostasis and Thrombosis, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA.
Thrombosis and Haemostasis (Impact Factor: 5.76). 10/2004; 92(3):478-85. DOI: 10.1267/THRO04090478
Source: PubMed

ABSTRACT Insights into hemostasis and thrombosis have historically benefited from the astute diagnosis of human bleeding and thrombotic disorders followed by decades of careful biochemical characterization. This work has set the stage for the development of a number of mouse models of hemostasis and thrombosis generated by gene targeting strategies in the mouse genome. The utility of these models is the in depth analysis that can be performed on the precise molecular interactions that support hemostasis and thrombosis along with efficacy testing of various therapeutic strategies. Already the mouse has proven to be an excellent model of the processes that support hemostasis and thrombosis in the human vasculature. A brief summary of the salient phenotypes from knockout mice missing key platelet receptors is presented, including the glycoprotein (GP) Ib-IX-V and GP IIb/IIIa (alphaIIb/beta3) receptors; the collagen receptors, GP VI and alpha2/beta1; the protease activated receptors (PARs); and the purinergic receptors, P2Y(1) and P2Y(12). A few differences exist between mouse and human platelets and where appropriate those will be highlighted in this review. Concluding remarks focus on the importance of understanding the power and limitations of various in vitro, ex vivo and in vivo models currently being used and the impact of the mouse strain on the described platelet phenotype.

0 Followers
 · 
61 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Atherosclerosis and its thrombotic complications are responsible for remarkably high numbers of deaths. The combination of in vitro, ex vivo, and in vivo experimental approaches has largely contributed to a better understanding of the mechanisms underlying the atherothrombotic process. Indeed, different animal models have been implemented in atherosclerosis and thrombosis research in order to provide new insights into the mechanisms that have already been outlined in isolated cells and protein studies. Yet, although no model completely mimics the human pathology, large animal models have demonstrated better suitability for translation to humans. Indeed, direct translation from mice to humans should be taken with caution because of the well-reported species-related differences. This paper provides an overview of the available atherothrombotic-like animal models, with a particular focus on large animal models of thrombosis and atherosclerosis, and examines their applicability for translational research purposes as well as highlights species-related differences with humans.
    BioMed Research International 01/2011; 2011:907575. DOI:10.1155/2011/907575 · 2.71 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Experimental models of thrombosis are important research resources that have helped to increase our understanding and knowledge of the pathogenesis of the atherothrombotic process as well as to develop novel therapeutic approaches. In fact, different animal models and procedures have been implemented in thrombosis research in order to provide new insights into the mechanisms that have already been outlined in isolated cells and protein studies. Moreover, animal preclinical studies have rendered a solid rationale for conducting prospective randomized trials in patients with coronary artery disease.
    Revue d& apos Electroencephalographie et de Neurophysiologie Clinique 5(2):194-202. DOI:10.1007/978-1-59745-285-4_39
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Platelets play a central role in hemostasis and thrombosis but also in the initiation of atherosclerosis, making platelet receptors and their intracellular signaling pathways important molecular targets for antithrombotic and anti-inflammatory therapy. Historically, much of the knowledge about hemostasis and thrombosis has been derived from patients suffering from bleeding and thrombotic disorders and the identification of the underlying molecular defects. In recent years, the availability of genetically modified mouse strains with defined defects in platelet function and the development of in vivo models to assess platelet-related physiologic and pathophysiologic processes have opened new ways to identify the individual roles and the interplay of platelet proteins in adhesion, activation, aggregation, secretion, and procoagulant activity in vitro and in vivo. This review will summarize key findings made by these approaches and discuss them in the context of human disease.
    Journal of Thrombosis and Haemostasis 09/2005; 3(8):1725-36. DOI:10.1111/j.1538-7836.2005.01488.x · 5.55 Impact Factor

Preview

Download
0 Downloads
Available from