Patzelt J, Mueller K A L, Breuning S, Karathanos A, Schleicher R, Seizer P, Gawaz M, Langer H F, Geisler T
Section for Cardioimmunology, Eberhard-Karls University Tuebingen, 72076 Tuebingen, Germany; University Hospital, Department of Cardiovascular Medicine, Eberhard-Karls University Tuebingen, 72076 Tuebingen, Germany.
University Hospital, Department of Cardiovascular Medicine, Eberhard-Karls University Tuebingen, 72076 Tuebingen, Germany.
Atherosclerosis. 2015 Feb;238(2):289-95. doi: 10.1016/j.atherosclerosis.2014.12.002. Epub 2014 Dec 18.
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.
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.
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.
抑制补体系统的成分或其受体已被假定为动脉粥样硬化一级和二级预防的一种理念，并已应用于临床试验。虽然过敏毒素受体C3aR和C5aR通常与炎症细胞相关，但体外研究表明它们也在血小板上表达。
采用流式细胞术检测了302例有冠状动脉疾病（CAD）记录患者群体中C3aR和C5aR的表达水平，这些患者包括稳定型CAD患者（n = 152）、不稳定型心绞痛患者（n = 54）、急性心肌梗死（AMI；非ST段抬高型心肌梗死，n = 70，ST段抬高型心肌梗死，n = 26）或健康对照者（n = 21）。与健康对照者相比，稳定型CAD、不稳定型心绞痛或AMI患者血小板上C5aR的表达显著更高（平均荧光强度分别为14.68（5.2）、14.56（5.18）和13.34（4.52），而健康对照者为10.68（3.1）；p < 0.001）。相比之下，与对照组相比，稳定型和不稳定型CAD患者血小板上C3aR的表达显著增强，但AMI患者没有。虽然这些受体的可溶性配体C3a和C5a之间存在强相关性，但我们观察到它们与血小板上的受体只有弱相关性。同样，激动剂诱导的聚集（MEA、ADP和TRAP）与血小板上过敏毒素受体的表达水平也只有弱相关性。值得注意的是，血小板上两种过敏毒素受体的表达与用表面活化标志物P-选择素评估的血小板活化密切相关（C3aR的r = 0.47，p > 0.001；C5aR的r = 0.76，p < 0.001）。同样，我们观察到C3aR与其他与血小板活化相关的分子如SDF-1呈正相关。
总之，我们观察到CAD患者中过敏毒素受体C3aR和C5aR的表达与血小板活化之间存在正相关。需要进一步研究来探讨这些发现的临床和机制相关性。
