Role of NF-κB in Platelet Function

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.

Adipokines and Inflammation: Focus on Cardiovascular Diseases

“…In patients with CAD, circulating levels of chemerin also correlate with the severity of CAD [ 129 , 130 , 131 , 132 ]. Some studies carried out in HUVECs have shown that chemerin participates in endothelial inflammation by inducing nuclear factor-κB (NF-κB), which is a key player in vascular inflammation, atherosclerosis development, and its pathological complications in atherothrombotic diseases [ 133 , 134 ] and the monocyte–endothelial adhesion [ 135 ]. In human VSMCs, chemerin has pro-apoptotic, pro-inflammatory, and proliferative effects that are mediated by nicotinamide adenine dinucleotide phosphate oxidase (Nox) activation and redox-sensitive mitogen-activated protein kinases signalling [ 136 ].…”

Regulation of Human Platelet Activation and Prevention of Arterial Thrombosis in Mice by Auraptene through Inhibition of NF-κB Pathway

“…CVDs are often caused by thrombotic events such as coronary heart disease. Platelets are major players in the occurrence of CVDs since they are involved in various thrombo-inflammatory diseases, particularly atherosclerosis and its progression to atherothrombosis in acute coronary syndrome (ACS) patients [ 1 ]. In fact, platelets control key hemostasis and formation of thrombosis, nevertheless, thrombosis can become pathological when it occurs, predominantly after the rupture of an atherosclerotic plaque.…”

“…Of the two subunits (IκBα and IκBβ), IκBα is the most represented. Upon activation, the IκB kinase (IKK) complex phosphorylates IκB causing its proteasome-mediated degradation, releasing NF-κB for nuclear translocation to exert its roles as a transcription factor for transcription of pro-inflammatory and pro-survival genes [ 1 ]. In such cellular settings, the role of NF-κB is genomic and well documented in nucleated cells.…”

Allium macrostemon Saponin Inhibits Activation of Platelet via the CD40 Signaling Pathway

“…In addition, the CD40L/CD40 complex induces activation of nuclear factor kappa B (NF-κB), which involves both IKK and IKB in the NF-κB signaling pathway. The latter exhibits a different non-genomic function in macrostemon platelets and induces inflammation and thrombosis ( Hachem et al, 2012 ; Karim et al, 2015 ; Paul et al, 2017 ; Xu et al, 2017 ; Kojok et al, 2019 ). In addition, the conjugation of TRAF protein (E3 ligase) with the CD40 receptor plays an important role in the CD40L/CD40 pathway, by mediating the activation of the canonical and non-canical NF-κB pathways as well as the MAPK pathway in response to CD40 ( Hadweh et al, 2014 ; de Jong et al, 2016 ; El Hokayem et al, 2017 ; Chen et al, 2018 ; Seijkens et al, 2018 ; Johansson et al, 2019 ; Unsworth et al, 2019 ).…”