The complexity of platelet metabolism and its contribution to atherothrombosis.
Platelet functions are multiple, complex and not limited to haemostasis. In fact, platelets play a relevant role in vascular inflammation and atherosclerosis (ATS). In the presence of vascular lesions or inflammation, endothelial denudation or activation triggers mechanisms that render the circulating platelets adhesive for the vascular wall. Endothelial lesions expose subendothelial matrix components, such as collagen, von Willebrand factor, fibronectin and other adhesive proteins. Platelet adhesion depends on the interaction between these components and platelet receptors (mainly glycoprotein (GP) VI and GPlb-IX-V). Adhesion triggers the platelet release of inflammatory and mitogenic substances that alter the thromboresistant endothelial surface, enhance the chemoattraction of leukocytes, stimulate smooth muscle cell proliferation and contribute to matrix degradation. Finally, GPIIb-IIIa receptors are activated, leading to firm platelet aggregation and thrombus formation. Platelets participate in the formation of mural thrombi in the late stages of atherosclerotic disease, but also adhere to endothelial cells during the earlier stages of atherosclerotic plaque development. Moreover, platelets exert important functions in modulating inflammatory and immune processes. An improved comprehension of the complex platelet pathophysiology could suggest new therapeutic strategies to reduce the impact of atherosclerotic disease.
Puddu
Paolo
P
Department of Internal Medicine, Ageing and Nephrological Diseases, University of Bologna and S. Orsola-Malpighi Hospital, Bologna, Italy.
Muscari
Antonio
A
Puddu
Giovanni M
GM
Cravero
Eleonora
E
Giannoni
Claudia
C
Zoli
Marco
M
D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000150:complications*; D001792:Blood Platelets / Q000378:metabolism*; D006801:Humans; D010974:Platelet Aggregation / Q000502:physiology; D011379:Prognosis; D012307:Risk Factors; D013927:Thrombosis / Q000097:blood* / Q000209:etiology