Abstract

Platelets are megakaryocyte-derived fragments lacking nuclei and prepped to maintain primary hemostasis by initiating blood clots on injured vascular endothelia. Pathologically, platelets undergo the same physiological processes of activation, secretion, and aggregation yet with such pronouncedness that they orchestrate and make headway the progression of atherothrombotic diseases not only through clot formation but also via forcing a pro-inflammatory state. Indeed, nuclear factor-κB (NF-κB) is largely implicated in atherosclerosis and its pathological complication in atherothrombotic diseases due to its transcriptional role in maintaining pro-survival and pro-inflammatory states in vascular and blood cells. On the other hand, we know little on the functions of platelet NF-κB, which seems to function in other non-genomic ways to modulate atherothrombosis. Therein, this review will resemble a rich portfolio for NF-κB in platelets, specifically showing its implications at the levels of platelet survival and function. We will also share the knowledge thus far on the effects of active ingredients on NF-κB in general, as an extrapolative method to highlight the potential therapeutic targeting of NF-κB in coronary diseases. Finally, we will unzip a new horizon on a possible extra-platelet role of platelet NF-κB, which will better expand our knowledge on the etiology and pathophysiology of atherothrombosis.

Highlights

  • Cardiovascular disease is the largest cause of death globally

  • Platelets are major players in the occurrence of cardiovascular diseases since they are involved in various thrombo-inflammatory diseases, atherosclerosis and its progression to atherothrombosis in acute coronary syndrome (ACS) patients [2,3,4,5]

  • We showed that sCD40L, in the presence of sub-optimal doses of platelet agonists like collagen and thrombin, significantly increased platelet activation and aggregation through an nuclear factor-κB (NF-κB)-independent CD40/TRAF-2/Rac-1/p38 MAPK axis [9]

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Summary

Introduction

Cardiovascular disease is the largest cause of death globally. According to the report from the World Health Organization (WHO), the death rate caused by cardiovascular diseases worldwide is estimated at 17.3 million people in 2008, accounting for 30% of deaths globally. The “inside-out” signaling of the αIIbβ integrin, in response to platelet activation, leads to platelet aggregation thanks to the binding of αIIbβ to fibrinogen promoting the formation of a thrombus [6,7]. Such a process could induce a partial or complete occlusion of the blood vessel, which leads to a decrease or blockage of the blood flow and becomes a cause of occurrence of ischemia or infarction of an irrigated organ such as the heart. We will widen our compass to include a potential extra-platelet role of platelet NF-κB, which might oblige us to modify our understanding of the role of platelets and of the progression of atherothrombotic diseases

The Genomic Role of NF-κB
Platelet Survival and Apoptosis
Platelet Activation and Priming
Thrombin-Activated Platelets
Collagen-Activated Platelets
CD40L-Primed Platelets
TLR Ligand-Activated Platelets
AGE-Activated Platelets
Epinephrine-Primed Platelets
ADP-Activated Platelets
Platelet Aggregation
Findings
Conclusions
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