ABSTRACT
Activated platelets and neutrophils exacerbate atherosclerosis. Platelets release the chemokines CXCL4, CXCL4L1 and CCL5, whereas myeloperoxidase (MPO) and azurocidin are neutrophil-derived. We investigated whether plasma levels of these platelet and neutrophil mediators are affected by the acute coronary syndrome (ACS), its medical treatment, concomitant clinical or laboratory parameters, and predictive for the progression of coronary artery disease (CAD). In an observational study, the association of various factors with plasma concentrations of platelet chemokines and neutrophil mediators in 204 patients, either upon admission with ACS and 6 hours later or without ACS or CAD, was determined by multiple linear regression. Mediator release was further analysed after activation of blood with ACS-associated triggers such as plaque material. CXCL4, CXCL4L1, CCL5, MPO and azurocidin levels were elevated in ACS. CXCL4 and CCL5 but not CXCL4L1 or MPO were associated with platelet counts and CRP. CXCL4 (in association with heparin treatment) and MPO declined over 6 hours during ACS. Elevated CCL5 was associated with a progression of CAD. Incubating blood with plaque material, PAR1 and PAR4 activation induced a marked release of CXCL4 and CCL5, whereas CXCL4L1 and MPO were hardly or not altered. Platelet chemokines and neutrophil products are concomitantly elevated in ACS and differentially modulated by heparin treatment. CCL5 levels during ACS predict a progression of preexisting CAD. Platelet-derived products appear to dominate the inflammatory response during ACS, adding to the emerging evidence that ACS per se may promote vascular inflammation.
Subject(s)
Acute Coronary Syndrome/diagnosis , Blood Platelets/metabolism , Chemokines/blood , Inflammation Mediators/blood , Inflammation/diagnosis , Acute Coronary Syndrome/blood , Acute Coronary Syndrome/drug therapy , Acute Coronary Syndrome/genetics , Acute Coronary Syndrome/immunology , Aged , Anticoagulants/therapeutic use , Antimicrobial Cationic Peptides/blood , Biomarkers/blood , Blood Platelets/drug effects , Blood Platelets/immunology , Blood Proteins , Carrier Proteins/blood , Case-Control Studies , Chemokine CCL5/blood , Chemokine CCL5/genetics , Chemokines/genetics , Disease Progression , Dose-Response Relationship, Drug , Female , Heparin/therapeutic use , Humans , Inflammation/blood , Inflammation/immunology , Linear Models , Male , Middle Aged , Neutrophils/drug effects , Neutrophils/immunology , Neutrophils/metabolism , Peroxidase/blood , Platelet Count , Polymorphism, Single Nucleotide , Predictive Value of Tests , Prognosis , Prospective Studies , Time FactorsABSTRACT
In recent years, it has become clear that platelets and platelet-derived chemokines, beyond their role in thrombosis and haemostasis, are important mediators affecting a broad spectrum of (patho)physiological conditions. These biologically active proteins are released from α-granules upon platelet activation, most probably even during physiological conditions. In this review, we give a concise overview and an update on the current understanding of platelet-derived chemokines in a context of health and disease.
