Platelets in the onset of atherosclerosis
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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2021, Blood ReviewsCitation Excerpt :Consequently, platelets are critical to the initiation mechanisms involved in atheromatous development and progression [56,57]. The first stage in the development of atherosclerosis is characterised by local endothelial activation that platelets contribute to by adhering to vascular cells, even before the presence of lesions [55,58,59]. Platelets proceed to induce the secretion of various chemokines in several types of vascular wall cells and platelets themselves (Table 1) [60].
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