Platelet factor 4 localization in carotid atherosclerotic plaques: correlation with clinical parameters

Abstract

Emerging evidence supports a role for platelets in the progression of atherosclerosis in addition to an involvement in thrombotic vascular occlusion. Platelet Factor 4 (PF4), a chemokine released by activated platelets, stimulates several pro-atherogenic processes. Therefore, we examined the localization of PF4 and the homologous protein, Neutrophil Activating Protein-2 (NAP-2) in lesions representing the evolution of human atherosclerotic plaques. Carotid plaques from 132 patients with critical carotid stenosis and 6 autopsy specimens were studied. Clinical, histologic and immunohistochemical data were analyzed using a chi(2)-test. PF4 was detected in the cytoplasm of luminal and neovascular endothelium, in macrophages and in regions of plaque calcification. The presence of PF4 in macrophages and neovascular endothelium correlated with lesion grade (p = 0.004; p = 0.044). Staining of macrophages for PF4 correlated with the presence of symptomatic atherosclerotic disease (p = 0.028). In early lesions, PF4 was commonly found in macrophages of early lesions (Grade I/II), whereas NAP-2 was rarely present. In conclusion, correlation between PF4 deposition, lesion severity and symptomatic atherosclerosis suggests that persistent platelet activation may contribute to the evolution of atherosclerotic vascular lesions. These studies support the rationale for the chronic use of anti-platelet therapy in patients at risk for developing symptomatic atherosclerosis.

Platelets, inflammation and anti-inflammatory effects of antiplatelet drugs in ACS and CAD

“…PF4 directly contributes to proatherogenic actions by promoting retention of lipoproteins (12). PF4 also interacts directly with oxidised low-density lipoprotein (oxLDL) leading to an induction of endothelial cell activation and dysfunction, macrophage foam cell formation, and VSMC migration and proliferation (13). Vascular wall cells express several SRs on their surface that mediate cellular effects of oxLDL.…”

“…Macrophages internalise apoptotic cell fragments, bacterial endotoxins, and oxLDL, leading to lipid accumulation and foam cell formation. Interestingly, PF4 in macrophages correlates with the presence and the extension of atherosclerotic lesions (13,14). CD40 ligand (CD40L, CD154) and its receptor CD40 are costimulatory molecules of the tumour necrosis factor (TNF) and TNF receptor family.…”

Chemokines in vascular pathology (Review)

“…Pitsilos et al detected PF4 in the cytoplasm of luminal and neovascular endothelium, in macrophages and in regions of plaque calcification. 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).…”

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

“…In histopathological study on human carotid atherosclerotic, PF-4 accumulates within macrophages of the plaque in the early lesion and continues to accumulate in foam cells and neovascular endothelial cells as lesion progressed (Pitsilos et al, 2003). PF-4 is deposited on the endothelial cell surface and retained by subendothelial proteoglycan (Aidoudi & Bikfalvi, 2010).…”