Open AccessCirculating Myeloid‐Related Protein –8/14 is Related to Thromboxane‐Dependent Platelet Activation in Patients With Acute Coronary Syndrome, With and Without Ongoing Low‐Dose Aspirin Treatment
Author(s) -
Santilli Francesca,
Paloscia Leonardo,
Liani Rossella,
Di Nicola Marta,
Di Marco Massimo,
Lattanzio Stefano,
La Barba Sara,
Pascale Silvia,
Mascellanti Marco,
Davì Giovanni
Publication year - 2014
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.114.000903
Subject(s) - medicine , aspirin , platelet activation , platelet , thromboxane b2 , acute coronary syndrome , urinary system , thromboxane , thromboxane a2 , gastroenterology , cardiology , myocardial infarction
Background Platelet activation is involved in acute coronary syndromes ( ACS ). Incomplete suppression by low‐dose aspirin treatment of thromboxane ( TX ) metabolite excretion (urinary 11‐dehydro‐ TXB 2 ) is predictive of vascular events in high‐risk patients. Myeloid‐related protein ( MRP )‐8/14 is a heterodimer secreted on activation of platelets, monocytes, and neutrophils, regulating inflammation and predicting cardiovascular events. Among platelet transcripts, MRP ‐14 has emerged as a powerful predictor of ACS . Methods and Results We enrolled 68 stable ischemic heart disease ( IHD ) and 63 ACS patients, undergoing coronary angiography, to evaluate whether MRP ‐8/14 release in the circulation is related to TX ‐dependent platelet activation in ACS and IHD patients and to residual TX biosynthesis in low‐dose aspirin–treated ACS patients. In ACS patients, plasma MRP ‐8/14 and urinary 11‐dehydro‐ TXB 2 levels were linearly correlated ( r =0.651, P <0.001) but significantly higher than those in IHD patients ( P =0.012, P =0.044) only among subjects not receiving aspirin. In aspirin‐treated ACS patients, MRP ‐8/14 and 11‐dehydro‐ TXB 2 were lower versus those not receiving aspirin ( P <0.001) and still significantly correlated ( r =0.528, P <0.001). Higher 11‐dehydro‐ TXB 2 significantly predicted higher MRP ‐8/14 in both all ACS patients and ACS receiving aspirin ( P <0.001, adj R 2 =0.463 and adj R 2 =0.497) after multivariable adjustment. Conversely, plasma MRP ‐8/14 ( P <0.001) and higher urinary 8‐iso‐prostaglandin F 2α ( P =0.050) levels were significant predictors of residual, on‐aspirin, TX biosynthesis in ACS (adjusted R 2 =0.384). Conclusions Circulating MRP ‐8/14 is associated with TX ‐dependent platelet activation in ACS , even during low‐dose aspirin treatment, suggesting a contribution of residual TX to MRP ‐8/14 shedding, which may further amplify platelet activation. Circulating MRP ‐8/14 may be a target to test different antiplatelet strategies in ACS .