title: Circulating 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.
abstract: 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-TXB2) 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.
  
  
  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-TXB2 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-TXB2 were lower versus those not receiving aspirin (P<0.001) and still significantly correlated (r=0.528, P<0.001). Higher 11-dehydro-TXB2 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 F2α (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.
authors.affiliation: Department of Medicine and Aging, University of Chieti "G. d'Annunzio" School of Medicine, Chieti, Italy (F.S., R.L., S.L., S.L.B., S.P., G.D.).
authors.forename: Francesca
authors.initials: F
authors.lastname: Santilli
authors.affiliation: Department of Cardiology, Civil Hospital Pescara, Pescara, Italy (L.P., M.D.M., M.M.).
authors.forename: Leonardo
authors.initials: L
authors.lastname: Paloscia
authors.affiliation: Department of Medicine and Aging, University of Chieti "G. d'Annunzio" School of Medicine, Chieti, Italy (F.S., R.L., S.L., S.L.B., S.P., G.D.).
authors.forename: Rossella
authors.initials: R
authors.lastname: Liani
authors.affiliation: Department of Experimental and Clinical Sciences, Biostatistics Laboratory, "G. d'Annunzio" University, Chieti, Italy (M.D.N.).
authors.forename: Marta
authors.initials: M
authors.lastname: Di Nicola
authors.affiliation: Department of Cardiology, Civil Hospital Pescara, Pescara, Italy (L.P., M.D.M., M.M.).
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Marco
authors.affiliation: Department of Medicine and Aging, University of Chieti "G. d'Annunzio" School of Medicine, Chieti, Italy (F.S., R.L., S.L., S.L.B., S.P., G.D.).
authors.forename: Stefano
authors.initials: S
authors.lastname: Lattanzio
authors.affiliation: Department of Medicine and Aging, University of Chieti "G. d'Annunzio" School of Medicine, Chieti, Italy (F.S., R.L., S.L., S.L.B., S.P., G.D.).
authors.forename: Sara
authors.initials: S
authors.lastname: La Barba
authors.affiliation: Department of Medicine and Aging, University of Chieti "G. d'Annunzio" School of Medicine, Chieti, Italy (F.S., R.L., S.L., S.L.B., S.P., G.D.).
authors.forename: Silvia
authors.initials: S
authors.lastname: Pascale
authors.affiliation: Department of Cardiology, Civil Hospital Pescara, Pescara, Italy (L.P., M.D.M., M.M.).
authors.forename: Marco
authors.initials: M
authors.lastname: Mascellanti
authors.affiliation: Department of Medicine and Aging, University of Chieti "G. d'Annunzio" School of Medicine, Chieti, Italy (F.S., R.L., S.L., S.L.B., S.P., G.D.).
authors.forename: Giovanni
authors.initials: G
authors.lastname: Davì
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood* / Q000188:drug therapy; D000368:Aged; D001241:Aspirin / Q000627:therapeutic use; D040501:Calgranulin A / Q000097:blood*; D040502:Calgranulin B / Q000097:blood*; D002908:Chronic Disease; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood* / Q000188:drug therapy; D015539:Platelet Activation; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine
chemical_list: D040501:Calgranulin A; D040502:Calgranulin B; D010975:Platelet Aggregation Inhibitors; C075750:8-epi-prostaglandin F2alpha; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D015237:Dinoprost; D001241:Aspirin
keywords: acute coronary syndrome; aspirin; platelets; platelet‐derived factors; thromboxane