title: Intra-plaque production of platelet-activating factor correlates with neoangiogenesis in human carotid atherosclerotic lesions.
abstract: Platelet-activating factor (PAF) is a phospholipid mediator synthesized by activated inflammatory and endothelial cells. Recently PAF has been shown to contribute to neoangiogenesis in several experimental models. Here we evaluated the presence of PAF and its potential role in neovascularization within human atherosclerotic plaques. The amount of PAF extracted from 18 carotid plaques (266.65+/-40.07 pg/100 mg dry tissue; mean +/- SE) was significantly higher than that extracted from 18 normal arterial specimens (6 from carotid artery and 12 from aorta) (4.72+/-2.31 pg/100 mg dry tissue; mean +/- SE). The levels of PAF significantly correlated with the infiltration of CD68-positive monocytes and the extent of neovascularization, detected as von Willebrand Factor-positive cells. The amount of PAF also correlated with the area occupied by TNF-alpha-expressing cells. The absence of enhanced level of PAF in the circulation of atherosclerotic patients suggests a local production of this mediator within the plaque. The lipid extracts of atherosclerotic plaques containing high levels of PAF-bioactivity, but not those of control arteries, were angiogenic in a murine Matrigel model. WEB 2170, a specific PAF receptor antagonist, significantly prevented angiogenesis induced by the lipid extracts of atherosclerotic plaques. Our results indicate a local production of PAF within the atherosclerotic plaques and suggest that it may contribute to intra-plaque neoangiogenesis.
authors.affiliation: Dipartimento di Fisiopatologia Clinica, Universitá degli Studi di Torino, Torino, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Lupia
authors.forename: Angela
authors.initials: A
authors.lastname: Pucci
authors.forename: Paolo
authors.initials: P
authors.lastname: Peasso
authors.forename: Maurizio
authors.initials: M
authors.lastname: Merlo
authors.forename: Paolo
authors.initials: P
authors.lastname: Baron
authors.forename: Cristina
authors.initials: C
authors.lastname: Zanini
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Del Sorbo
authors.forename: Simona
authors.initials: S
authors.lastname: Rizea-Savu
authors.forename: Luigi
authors.initials: L
authors.lastname: Silvestro
authors.forename: Marco
authors.initials: M
authors.lastname: Forni
authors.forename: Giorgio
authors.initials: G
authors.lastname: Emanuelli
authors.forename: Giovanni
authors.initials: G
authors.lastname: Camussi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Montrucchio
mesh_terms: D000328:Adult; D000368:Aged; D001161:Arteriosclerosis / Q000378:metabolism*; D002340:Carotid Artery Diseases / Q000378:metabolism*; D005260:Female; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D010972:Platelet Activating Factor; D014409:Tumor Necrosis Factor-alpha