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Endothelial derived vasoactive factors and leukocyte derived inflammatory mediators in subjects with asymptomatic
I Anwaar1, A Gottsäter, B Hedblad
1Department of Medicine, Lund University, University Hospital, Malmö, Sweden.
Insights
Leukocyte inflammatory mediators may inhibit platelet activation in atherosclerosis. This study found relationships between inflammatory markers and platelet cyclic nucleotides, suggesting a feedback mechanism to control platelet aggregation.
Area of Science:
- Cardiovascular Biology
- Inflammation Research
- Platelet Physiology
Background:
- Asymptomatic atherosclerosis involves complex interactions between endothelial function and inflammatory processes.
- Leukocyte-derived inflammatory mediators play a role in cardiovascular disease progression.
- Platelet activation is a critical component of the atherosclerotic inflammatory cascade.
Purpose of the Study:
- To investigate the relationship between endothelial function markers and leukocyte inflammatory mediators in asymptomatic atherosclerosis.
- To explore the association between intraplatelet cyclic nucleotides (cGMP, cAMP) and inflammatory markers.
Main Methods:
- Measured intraplatelet cyclic 3',5'-guanosine monophosphate (cGMP) and cyclic 3',5'-adenosine monophosphate (cAMP) in 197 subjects.
- Assessed plasma endothelin-1 (ET-1) and neopterin levels.
- Quantified neutrophil protease 4 (NP4), tumor necrosis factor (TNFmu), soluble tumor necrosis factor receptor-1 (sTNFR-1), and neutrophil gelatinase-associated lipocalin (NGAL) in a subset of subjects.
Main Results:
- A negative correlation was observed between intraplatelet cyclic guanosine monophosphate (cGMP) and plasma endothelin-1 (ET-1).
- Plasma neopterin and NP4 showed a positive correlation with intraplatelet cGMP.
- Intraplatelet cyclic adenosine monophosphate (cAMP) correlated positively with plasma TNFmu and sTNFR-1.
Conclusions:
- The findings suggest a potential anti-aggregating effect of leukocytes on platelets.
- This interaction may represent a negative feedback mechanism to modulate platelet activation in atherosclerosis.
- Understanding these relationships could offer insights into therapeutic strategies for atherosclerotic inflammation.
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.