Targeting Platelet in Atherosclerosis Plaque Formation: Current Knowledge and Future Perspectives

Abstract

Besides their role in hemostasis and thrombosis, it has become increasingly clear that platelets are also involved in many other pathological processes of the vascular system, such as atherosclerotic plaque formation. Atherosclerosis is a chronic vascular inflammatory disease, which preferentially develops at sites under disturbed blood flow with low speeds and chaotic directions. Hyperglycemia, hyperlipidemia, and hypertension are all risk factors for atherosclerosis. When the vascular microenvironment changes, platelets can respond quickly to interact with endothelial cells and leukocytes, participating in atherosclerosis. This review discusses the important roles of platelets in the plaque formation under pro-atherogenic factors. Specifically, we discussed the platelet behaviors under disturbed flow, hyperglycemia, and hyperlipidemia conditions. We also summarized the molecular mechanisms involved in vascular inflammation during atherogenesis based on platelet receptors and secretion of inflammatory factors. Finally, we highlighted the studies of platelet migration in atherogenesis. In general, we elaborated an atherogenic role of platelets and the aspects that should be further studied in the future.

Ultrastructural Study of Platelet Behavior and Interrelationship in Sprouting and Intussusceptive Angiogenesis during Arterial Intimal Thickening Formation

“…Platelet participation in several pathophysiological mechanisms involved in atherosclerosis, bypass stenosis, and restenosis is an important subject of research in human and experimental pathology [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. Platelets act in angiogenesis [ 15 , 16 , 17 , 18 ], which is one of the main pathophysiological mechanisms of this pathology.…”

CLEC-2-dependent platelet subendothelial accumulation by flow disturbance contributes to atherogenesis in mice

“…Platelets participate in the development of atherosclerosis by mediating interactions between platelets and leukocytes or between platelets and endothelial cells 32 , 33 . Of note, P-selectin on activated platelets or endothelial cells binds PSGL-1 on leukocytes especially neutrophils and monocytes, thereby promoting the leukocyte adhesion and transmigration during inflammation.…”

Where the Action Is—Leukocyte Recruitment in Atherosclerosis

“…While shear stress can trigger endothelial activation, leading to upregulation of adhesion molecules and chemokines (see section Keep it Flowing), shear stress is also known to directly trigger platelet activation and aggregation in atherosclerotic vessels, thus promoting thrombotic arterial occlusion ( 328 ). However, shear stress or shear activated EC can stimulate platelets also in earlier phases of atherogenesis and promote platelet adhesion to the EC surface via enhanced adhesion molecule expression or decreased release of NO and prostacyclin ( 329 ), thus shifting the balance between inhibitory and activating pathways in platelets in favor of platelet activation. Of interest, impaired function of the ATP-binding cassette transporter G4 in bone marrow megakaryocyte progenitors giving rise to platelets has been shown to inhibit cholesterol efflux from these cells, thus promoting platelet production and accelerating atherosclerosis ( 330 ).…”