title: Expression of anaphylatoxin receptors on platelets in patients with coronary heart disease.
abstract: OBJECTIVE
  Inhibition of components of the complement system or of its receptors has been postulated as a concept for primary and secondary prevention in atherosclerosis and was applied in clinical trials. Although the anaphylatoxin-receptors C3aR and C5aR are commonly associated with inflammatory cells, in vitro studies suggested their expression also on platelets.
  
  
  RESULTS
  Expression levels of C3aR and C5aR were measured by flow cytometry in a collective of 302 patients with documented coronary artery disease (CAD) including patients with stable CAD (n = 152), unstable angina (n = 54), acute myocardial infarction (AMI; Non-ST elevation myocardial infarction, n = 70, ST elevation MI, n = 26) or healthy controls (n = 21). Patients with stable CAD, unstable angina or AMI had significantly higher expression of C5aR on platelets in comparison to healthy controls (MFI 14.68 (5.2), 14.56 (5.18) and 13.34 (4.52) versus 10.68 (3.1)); p < 0.001). In contrast, the expression of C3aR on platelets was significantly enhanced in patients with stable and unstable CAD but not in patients with AMI compared to controls. While there was a strong correlation between the soluble ligands of these receptors C3a and C5a, we observed only a weak correlation with their receptors on platelets. Similarly, agonist induced aggregation (MEA, ADP, and TRAP) showed only a weak correlation with the expression level of anaphylatoxin - receptors on platelets. Of note, the expression of both anaphylatoxin-receptors on platelets strongly correlated with platelet activation as assessed with the surface activation marker P-selectin (r = 0.47, p > 0.001 for C3aR, r = 0.76 for C5aR, p < 0.001). Likewise, we observed a positive correlation of C3aR with other molecules associated with platelet activation such as SDF-1.
  
  
  CONCLUSIONS
  In summary, we observed a positive correlation between the expression of anaphylatoxin-receptors C3aR and C5aR with platelet activation in patients with CAD. Further investigations are needed to study the clinical and mechanistic relevance of these findings.
authors.affiliation: Section for Cardioimmunology, Eberhard-Karls University Tuebingen, 72076 Tuebingen, Germany; University Hospital, Department of Cardiovascular Medicine, Eberhard-Karls University Tuebingen, 72076 Tuebingen, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Patzelt
authors.affiliation: University Hospital, Department of Cardiovascular Medicine, Eberhard-Karls University Tuebingen, 72076 Tuebingen, Germany.
authors.forename: K A L
authors.initials: KA
authors.lastname: Mueller
authors.affiliation: University Hospital, Department of Cardiovascular Medicine, Eberhard-Karls University Tuebingen, 72076 Tuebingen, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Breuning
authors.affiliation: University Hospital, Department of Cardiovascular Medicine, Eberhard-Karls University Tuebingen, 72076 Tuebingen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Karathanos
authors.affiliation: Section for Cardioimmunology, Eberhard-Karls University Tuebingen, 72076 Tuebingen, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Schleicher
authors.affiliation: University Hospital, Department of Cardiovascular Medicine, Eberhard-Karls University Tuebingen, 72076 Tuebingen, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Seizer
authors.affiliation: University Hospital, Department of Cardiovascular Medicine, Eberhard-Karls University Tuebingen, 72076 Tuebingen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Gawaz
authors.affiliation: Section for Cardioimmunology, Eberhard-Karls University Tuebingen, 72076 Tuebingen, Germany; University Hospital, Department of Cardiovascular Medicine, Eberhard-Karls University Tuebingen, 72076 Tuebingen, Germany. Electronic address: harald.langer@med.uni-tuebingen.deor.
authors.forename: H F
authors.initials: HF
authors.lastname: Langer
authors.affiliation: University Hospital, Department of Cardiovascular Medicine, Eberhard-Karls University Tuebingen, 72076 Tuebingen, Germany. Electronic address: tobias.geisler@med.uni-tuebingen.de.
authors.forename: T
authors.initials: T
authors.lastname: Geisler
mesh_terms: D000368:Aged; D000789:Angina, Unstable / Q000097:blood; D001792:Blood Platelets / Q000737:chemistry*; D016022:Case-Control Studies; D003176:Complement C3 / Q000032:analysis; D015936:Complement C5a / Q000032:analysis; D003324:Coronary Artery Disease / Q000097:blood; D003327:Coronary Disease / Q000097:blood* / Q000175:diagnosis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008024:Ligands; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood; D010974:Platelet Aggregation; D010979:Platelet Function Tests; D044087:Receptor, Anaphylatoxin C5a / Q000097:blood*; D011951:Receptors, Complement / Q000097:blood*; D015854:Up-Regulation
chemical_list: C038245:C3 protein, human; C488033:C5AR1 protein, human; D003176:Complement C3; D008024:Ligands; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; C085567:complement C3a receptor; D015936:Complement C5a
keywords: Anaphylatoxin receptors; C3a; C5a; Coronary heart disease; Platelets