title: Endothelial derived vasoactive factors and leukocyte derived inflammatory mediators in subjects with asymptomatic atherosclerosis.
abstract: To clarify relationships between the (endothelial vasodilatory and vasoconstrictive function) and leukocyte inflammatory mediators in subjects with asymptomatic atherosclerosis, we measured (intraplatelet cyclic 3',5'-guanosine monophosphate [cGMP] and cyclic 3',5'-adenosine monophosphate [cAMP]), plasma endothelin (ET-1), and plasma neopterin in 197 subjects with asymptomatic atherosclerosis (median age 63 years, range 49-69 years). We measured neutrophil protease 4 (NP4), tumor necrosis factor (TNFmu), soluble tumor necrosis factor receptor-1 (sTNFR-1), and neutrophil gelatinase associated lipocalin (NGAL) in 152 of the 197 subjects. Intraplatelet cGMP correlated inversely with plasma ET-1 (r=-0.22; p=0.01), which confirms earlier in vitro data of the inhibitory effect of ET-1 on NO production and/or the cGMP mediated inhibitory effect of NO on ET-1 production. Plasma neopterin as well as NP4 correlated directly with intraplatelet cGMP (r=0.24; p<0.01 and r=0.33; p<0.001, respectively). Intraplatelet cAMP correlated directly with plasma TNFmu (r=0.17; p<0.05) and sTNFR-1 (r=0.20; p<0.05). The relationship between leukocyte derived inflammatory mediators and intraplatelet cyclic nucleotides suggest an antiaggregating effect of leukocytes upon platelets, which may constitute a negative feedback mechanism that inhibits platelet activation during the atherosclerotic inflammatory process.
authors.affiliation: Department of Medicine, Lund University, University Hospital, Malmö, Sweden.
authors.forename: I
authors.initials: I
authors.lastname: Anwaar
authors.forename: A
authors.initials: A
authors.lastname: Gottsäter
authors.forename: B
authors.initials: B
authors.lastname: Hedblad
authors.forename: B
authors.initials: B
authors.lastname: Palmqvist
authors.forename: I
authors.initials: I
authors.lastname: Mattiasson
authors.forename: F
authors.initials: F
authors.lastname: Lindgärde
mesh_terms: D000368:Aged; D001161:Arteriosclerosis / Q000097:blood* / Q000150:complications / Q000000981:diagnostic imaging; D001792:Blood Platelets / Q000378:metabolism; D017536:Carotid Artery, Common; D016893:Carotid Stenosis / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology; D000242:Cyclic AMP / Q000097:blood*; D006152:Cyclic GMP / Q000097:blood*; D016207:Cytokines / Q000097:blood; D019332:Endothelin-1 / Q000097:blood*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D053146:Myeloblastin; D019798:Neopterin / Q000097:blood*; D010974:Platelet Aggregation / Q000502:physiology; D011446:Prospective Studies; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000097:blood; D014463:Ultrasonography
chemical_list: D016207:Cytokines; D019332:Endothelin-1; D019798:Neopterin; D000242:Cyclic AMP; D012697:Serine Endopeptidases; D053146:Myeloblastin; D006152:Cyclic GMP