Platelets in the onset of atherosclerosis

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Abstract

Beyond their role in hemostasis and thrombosis platelets are critically involved in the onset of atherosclerosis. Platelets represent an important linkage between inflammation, and atherogenesis. Platelets interact with inflammatory cells including leukocytes and endothelium. These interactions lead to leukocyte recruitment towards the vascular wall, initiating extravasation of circulating mononuclear cells and foam cell generation. Inflammatory processes within the arterial wall result in development of atherosclerotic lesions and atheroprogression. Inhibition of platelet interaction with the arterial wall results in attenuation of atherosclerosis and may be a novel therapeutic strategy in treatment of high-risk patients.

Section snippets

Platelet–endothelium adhesion

Recently, it has become increasingly evident that endothelial denudation is not an absolute prerequisite to allow platelet attachment to the arterial wall. The intact, non-activated endothelium normally prevents platelet adhesion to the extracellular matrix. The adhesion receptors involved in platelet attachment to the subendothelial matrix, e.g., following rupture of an atherosclerotic plaque, have been well defined during the past decade, however, the molecular determinants that promote the

Platelet-derived mediators stimulate inflammation

During the adhesion process, platelets become activated and release an arsenal of potent inflammatory and mitogenic substances into the local microenvironment, thereby altering chemotactic, adhesive and proteolytic properties of endothelial cells [21]. These platelet-induced alterations of the endothelial phenotype support chemotaxis, adhesion and transmigration of monocytes to the site of inflammation.

Released from dense granules, α-granules, lysosomes, the canalicular system, or the cytosol,

Platelets in animal models of atherosclerosis

Abundant recent data support the concept of atherosclerosis to be a chronic inflammatory disease [44]. However, the contribution of platelets to the process of atherosclerosis was unclear for decades. With the help of intravital microscopy and the availability of appropriate atherosclerotic animal models, it has become evident that platelets adhere to the arterial wall in vivo even in the absence of endothelial cell denudation [45], [46]. Theilmeier and coworkers found in hypercholesterolemic

Conclusions

It has become clear that besides their role in hemostasis and thrombosis, platelets regulate a variety of inflammatory responses and are key players in atherothrombosis. Thrombosis and inflammation are therefore linked rather than separate entities. Because atherothrombotic diseases are the major cause of morbidity and mortality in developed countries, understanding the role of platelets for vascular inflammation and atherosclerosis is challenging. Major progress has been made to understand the

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