Endothelial expression of E-selectin is induced by the platelet-specific chemokine platelet factor 4 through LRP in an NF-κB–dependent manner

Abstract

The involvement of platelets in the pathogenesis of atherosclerosis has recently gained much attention. Platelet factor 4 (PF4), a platelet-specific chemokine released on platelet activation, has been localized to atherosclerotic lesions, including macrophages and endothelium. In this report, we demonstrate that Eselectin, an adhesion molecule involved in atherogenesis, is up-regulated in human umbilical vein endothelial cells exposed to PF4. Induction of E-selectin RNA is time and dose dependent. Surface expression of E-selectin, as measured by flow cytometry, is also increased by PF4. PF4 induces E-selectin expression by activation of transcriptional activity. Activation of nuclear factor-B is critical for PF4-induced E-selectin expression, as demonstrated by promoter activation studies and electrophoretic mobility shift assays. Further, we have identified the

A new role for NF-κB in angiogenesis inhibition

“…In addition, EMSA experiments demonstrate that PF4 treatment of HUVECs results in binding of NF-kB to its DNA-binding site already after 1 h of stimulation. 37 The angiostatic properties of angiostatin, a cleavage product of plasminogen, have also been linked with NF-kB. Chen et al 38 have analyzed the global action of angiostatin in endothelial cells.…”

“…49 This normalization has been correlated with upregulation in endothelial cells of ICAM-1, VCAM-1 and E-selectin. 37,50 Therefore, activation of NF-kB by angiostatic therapy has apparently not only a direct effect on endothelial cells but also an indirect effect via expression of adhesion molecules and subsequent reversal of endothelial cell anergy (Figure 1). In addition, we have recently described that galectin-1 is a receptor for anginex, and that this protein is crucial for tumor angiogenesis.…”

Chemokines in vascular pathology (Review)

“…The presence of PF4 in macrophages and neovascular endothelium significantly correlated with lesion grade (52). Furthermore, in a recent study, Yu et al demonstrated that E-selectin, an adhesion molecule involved in atherogenesis, is up-regulated in human umbilical vein endothelial cells exposed to PF4 (53). Finally, Nassar et al showed that PF4 bound to oxidized (ox)-LDL directly, and also increased ox-LDL binding to vascular cells and macrophages, thus demonstrating an alternative mechanism by which platelet activation at sites of vascular injury may promote the accumulation of deleterious lipoproteins (54).…”

Plaque, Platelets, and Plug – The Pathogenesis of Acute Coronary Syndrome

“…PF-4 is deposited on the endothelial cell surface and retained by subendothelial proteoglycan (Aidoudi & Bikfalvi, 2010). PF-4 can activate endothelial cells by stimulating E-selectin expression (Yu et al, 2005). In vitro study indicates that PF-4 inhibits apolipoprotein Bcontaining LDL catabolism and facilitates retension of LDL on cell surface (Sachais et al, 2002).…”