title: Platelet bound oxLDL shows an inverse correlation with plasma anaphylatoxin C5a in patients with coronary artery disease.
abstract: Both oxidized lipids as well as the complement system contribute to atherothrombosis. The expression of complement receptors correlates with the expression of platelet activation markers, and platelet bound oxidized low-density lipoprotein (oxLDL) modulates platelet function. In the present study, we investigated the relationship of markers of complement activation, the anaphylatoxins C5a and C3a, and oxidized low-density lipoprotein. Two hundred and seven patients with coronary artery disease (CAD) were analyzed in this study. Using enzyme-linked immunosorbent assays, plasma levels of oxLDL, C3a, and C5a were measured. Moreover, we assessed platelet bound oxLDL by flow cytometry. The overall level of C5a in the troponin negative group (stable angina (SA) and unstable angina (UA)) compared to the troponin positive group (non-ST-elevation myocardial infarction (NSTEMI) and ST-elevation myocardial infarction (STEMI)) did not differ significantly (62.7 ± 32.4 ng/ml versus 65.8 ± 40.3 ng/ml). While C5a and C3a showed a significant correlation with each other (r = 0.25, p < 0.001), there was no statistically significant relationship between C3a and platelet bound oxLDL (r = 0.06, p = 0.37). Furthermore, plasma oxLDL did not correlate with either C3a or C5a. However, we observed a moderate, yet significant negative correlation between plasma C5a and platelet bound oxLDL (r = -0.15, p = 0.04). Partial correlation analysis correcting for the presence of acute coronary syndrome (ACS), troponin status or the subgroups SA, UA, NSTEMI, or STEMI did not alter this correlation substantially. Interestingly, flow cytometric analysis of human platelets showed increased expression of C5aR and P-selectin after in vitro stimulation with oxLDL. In conclusion, the complement anaphylatoxin C5a shows an inverse correlation with platelet bound oxLDL. The relationship of oxidized lipids to particular complement components may add to the platelet-lipid interplay in atherogenesis and trigger future clinical and mechanistic studies.
authors.affiliation: a Department of Cardiology and Cardiovascular Medicine , Eberhard Karls-University Tübingen , Tübingen , Germany.|b Section for Cardioimmunology , Eberhard Karls-University Tübingen , Tübingen , Germany.
authors.forename: Henry
authors.initials: H
authors.lastname: Nording
authors.affiliation: a Department of Cardiology and Cardiovascular Medicine , Eberhard Karls-University Tübingen , Tübingen , Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Giesser
authors.affiliation: a Department of Cardiology and Cardiovascular Medicine , Eberhard Karls-University Tübingen , Tübingen , Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Patzelt
authors.affiliation: a Department of Cardiology and Cardiovascular Medicine , Eberhard Karls-University Tübingen , Tübingen , Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Sauter
authors.affiliation: a Department of Cardiology and Cardiovascular Medicine , Eberhard Karls-University Tübingen , Tübingen , Germany.|b Section for Cardioimmunology , Eberhard Karls-University Tübingen , Tübingen , Germany.
authors.forename: Frederic
authors.initials: F
authors.lastname: Emschermann
authors.affiliation: c Department of Cardiology , Centre of Internal Medicine, J.W. Goethe University Frankfurt, Frankfurt am Main , Germany.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Stellos
authors.affiliation: a Department of Cardiology and Cardiovascular Medicine , Eberhard Karls-University Tübingen , Tübingen , Germany.
authors.forename: Meinrad
authors.initials: M
authors.lastname: Gawaz
authors.affiliation: a Department of Cardiology and Cardiovascular Medicine , Eberhard Karls-University Tübingen , Tübingen , Germany.|b Section for Cardioimmunology , Eberhard Karls-University Tübingen , Tübingen , Germany.
authors.forename: Harald F
authors.initials: HF
authors.lastname: Langer
mesh_terms: D001792:Blood Platelets / Q000378:metabolism*; D015936:Complement C5a / Q000276:immunology*; D003324:Coronary Artery Disease / Q000097:blood* / Q000276:immunology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D019007:P-Selectin / Q000378:metabolism; D015539:Platelet Activation; D010974:Platelet Aggregation; D011485:Protein Binding
chemical_list: D008077:Lipoproteins, LDL; D019007:P-Selectin; C099252:oxidized low density lipoprotein; D015936:Complement C5a
keywords: Cardiovascular disease; complement system; oxLDL; platelets