Update on pathological platelet activation in coronary thrombosis

Abstract

Although coronary thrombosis (CT) is integral to cardiovascular outcomes, the underlying pathophysiological mechanisms remain unclear. CT may occur in case of atherosclerotic plaque erosion/rupture, or even after stenting implantation. Platelets (PLT) activation is the keystone of atherothrombosis and depends on many dysregulated elements, including endothelial dysfunction, oxidized lipoproteins, and immune response. Besides the classical view of PLT as an effector of hemostatic response, a new repertoire of PLT activities is emerging. PLT lipidome oxidation is a self‐maintaining process which promotes PLT reactivity, coagulation cascade, and inflammatory cell activation. PLT‐innate immune cell interaction is also sustained by neutrophil extracellular traps and NLRP3 inflammasome pathways. Other noteworthy emerging mechanisms are implicated in the crosstalk between PLT and surrounding cells. Especially, microvesicles (MVs) released from PLT may extend their signaling network far beyond the classical cell−cell interactions. Moreover, the recognition of noncoding RNA in PLT MVs introduce another layer of complexity in terms of intercellular signaling by a direct regulation of messenger RNA profile and gene expression in the recipient cells. The aim of this narrative review is to update the recent advance in CT and intracoronary stent thrombosis, including causal factors and potential translation of experimental evidence into the clinical setting.

High glucose mediates NLRP3 inflammasome activation via upregulation of ELF3 expression

“…Hyperglycaemia-mediated endothelial dysregulation has been recognized as a potential target for the treatment of cardiovascular disorders in patients with diabetes 15 . NLRP3 inflammasome activation has been shown to be involved in the pathogenesis of cardiovascular disease and vascular endothelial dysfunction 6 . IL-1β and IL-18, two key cytokines regulated by NLRP3 inflammasome activation, participate in endothelial inflammation and cardiovascular disease in humans 7,[16][17][18][19] .…”

“…Endothelial NLRP3 inflammasome activation mediates endothelial inflammation 4,5 , thus resulting in vascular endothelial injury in hyperglycaemia 6 . The characteristics of the subjects are shown in Table 1.…”

“…Activation of the NOD-like receptor pyrin domain 3 (NLRP3) inflammasome leads to the generation of bioactive interleukin (IL)-1β and IL-18 4,5 , thus participating in endothelial inflammation and cardiovascular complications 6 . The NLRP3 inflammasome consists of three parts: NLRP3, caspase-1, and apoptosis-associated speck-like protein (ASC).…”

Comparison of First- and Second-Generation Drug-Eluting Stents in Patients with Acute Myocardial Infarction and Prediabetes Based on the Hemoglobin A1c Level

“…Liu et al [29] suggested that elevated glucose level is associated with the development of endothelial dysfunction. Moreover, this endothelial dysfunction is the leading cause of platelet activation [30]. In addition, hyperglycemia plays an important role in the development of diabetic macrovascular complications, including atherosclerosis and restenosis [31].…”

Platelet lipidome: Dismantling the “Trojan horse” in the bloodstream

“…This “Trojan horse” of lipid repertoire is overlooked in the conventional lipid profile but has profound pathophysiological significance. Platelets can deliver atherogenic lipids while seeding atheroprogression and contribute to chronic manifestations of cardiovascular disease (CVD) . Lately, advanced lipidomic analyses have started to unravel the multifaceted aspects of the platelet lipidome .…”