Endothelial derived vasoactive factors and leukocyte derived inflammatory mediators in subjects with asymptomatic atherosclerosis

To clarify relationships between the (endothelial vasodilatory and vasocons trictive function) and leukocyte inflammatory mediators in subjects with as ymptomatic atherosclerosis, we measured (intraplatelet cyclic 3-5C guanosin e monophosphate [cGMP] and cyclic 3-5C adenosine monophosphate [cAMP]), pla sma endothelin (ET-1), and plasma neopterin in 197 subjects with asymptomat ic atherosclerosis (median age 63 years, range 49-69 years). We measured ne utrophil protease 4 (NP4), tumor necrosis factor (TNF mu), soluble tumor ne crosis factor receptor-1 (sTNFR-1), and neutrophil gelatinase associated li pocalin (NGAL) in 152 of the 197 subjects. Intraplatelet cGMP correlated in versely 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 med iated 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 pla sma TNF mu (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 n ucleotides suggest an antiaggregating effect of leukocytes upon platelets, which may constitute a negative feedback mechanism that inhibits platelet a ctivation during the atherosclerotic inflammatofy process.