HomeCirculation ResearchVol. 113, No. 9Role of NF-κB Pathway on Platelet Activation Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBRole of NF-κB Pathway on Platelet Activation Mirta Schattner Mirta SchattnerMirta Schattner Laboratory of Experimental Thrombosis, Institute of Experimental Medicine-CONICET, National Academy of Medicine, Buenos Aires, Argentina Search for more papers by this author Originally published12 Oct 2013https://doi.org/10.1161/CIRCRESAHA.113.302333Circulation Research. 2013;113:e92To the Editor:I have read with great interest the review by Rondina et al1 on “Platelets as Cellular Effectors of Inflammation in Vascular Diseases” recently published in the Circulation Research Journal.1 Although I consider that it is a detailed and updated review on the role of platelets in the inflammatory and immune response, I am surprised by the vague and partial information about the expression and nongenomic role of the nuclear transcription factor-kappa B (NF-κB) in platelets.The authors mention that platelets express several NF-κB proteins and that a complex of NF-κB, inhibitor of κB, and protein kinase A was reported to exert negative feedback activities that modulate cytoskeletal reorganization and aggregation in platelets stimulated by thrombin or collagen. The references for this concept are the articles of Gambaryan et al2 and Spinelli et al.3,4Remarkably, the study of Spinelli et al,3 instead of showing a negative regulatory effect of NF-κB, claims the opposite. In fact, in the last sentence of the abstract, it is written “On the basis of these data, NF-κB is also identified as a new target to dampen unwanted platelet activation.” The second article of Spinelli et al is just an editorial comment of the article published by Gambaryan et al.2More important still, there is no mention of 7 other articles,5–11 including a pioneer work from our group,5 describing an opposite effect of NF-κB activation in platelets. In fact, using different strategies (including IkB kinase β knockout mice), these studies show that activation of NF-κB pathway promotes platelet activation.Furthermore, the study of Wei et al9 shows an interesting dual regulatory role of NF-κB on platelet activation. Although NF-κB activation initiates platelet activation, it also seems to be necessary for activated platelets to shed their surface glycoproteins. More specifically, NF-κB activation promotes a disintegrin and metalloprotease domain 17 (ADAM17)-mediated glycoprotein Ibα (GPIbα) shedding, limiting platelet interactions with leukocytes.Simultaneously with the publication of the review by Rondina et al,1 Karim et al,12 using IkB kinaseβ knockout mice, show that IkB kinase phosphorylation of synaptosomal associated protein (SNAP)-23 controls platelet secretion. Collectively, all these data support the notion that NF-κB activation is increasingly recognized as a new signaling pathway in the regulation of platelet biology. However, it is clear that the underlying mechanisms of NF-κB function still remain to be established.Mirta SchattnerLaboratory of Experimental ThrombosisInstitute of Experimental Medicine-CONICETNational Academy of MedicineBuenos Aires, Argentina