title: Inflammatory role and prognostic value of platelet chemokines in acute coronary syndrome.
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.
authors.forename: X
authors.initials: X
authors.lastname: Blanchet
authors.forename: K
authors.initials: K
authors.lastname: Cesarek
authors.forename: J
authors.initials: J
authors.lastname: Brandt
authors.forename: H
authors.initials: H
authors.lastname: Herwald
authors.forename: D
authors.initials: D
authors.lastname: Teupser
authors.forename: H
authors.initials: H
authors.lastname: Küchenhoff
authors.forename: E
authors.initials: E
authors.lastname: Karshovska
authors.forename: S F
authors.initials: SF
authors.lastname: Mause
authors.forename: W
authors.initials: W
authors.lastname: Siess
authors.forename: H
authors.initials: H
authors.lastname: Wasmuth
authors.forename: O
authors.initials: O
authors.lastname: Soehnlein
authors.forename: R R
authors.initials: RR
authors.lastname: Koenen
authors.forename: C
authors.initials: C
authors.lastname: Weber
authors.affiliation: Dr. Philipp von Hundelshausen, Institute for Cardiovascular Prevention, Ludwig-Maximilians University (LMU), Pettenkoferstr. 9, 80336 Munich, Germany, Tel.: +49 89 5160 4359, Fax: +49 89 5160 4352, E-mail: phundels@med.lmu.de.
authors.forename: P
authors.initials: P
authors.lastname: von Hundelshausen
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use; D023181:Antimicrobial Cationic Peptides / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D001798:Blood Proteins; D002352:Carrier Proteins / Q000097:blood; D016022:Case-Control Studies; D018946:Chemokine CCL5 / Q000097:blood / Q000235:genetics; D018925:Chemokines / Q000097:blood* / Q000235:genetics; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D018836:Inflammation Mediators / Q000097:blood*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009195:Peroxidase / Q000097:blood; D010976:Platelet Count; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D013997:Time Factors
chemical_list: C062991:AZU1 protein, human; D000925:Anticoagulants; D023181:Antimicrobial Cationic Peptides; D015415:Biomarkers; D001798:Blood Proteins; C483024:CCL5 protein, human; D002352:Carrier Proteins; D018946:Chemokine CCL5; D018925:Chemokines; D018836:Inflammation Mediators; D006493:Heparin; D009195:Peroxidase
keywords: Acute coronary syndrome; atherosclerosis; chemokines; neutrophils; platelets