Division of Cardiovascular & Diabetes Research, Leeds Institute of Genetics Health & Therapeutics, University of Leeds, UK.
Diab Vasc Dis Res. 2012 Jul;9(3):216-25. doi: 10.1177/1479164111432788. Epub 2012 Jan 17.
Increased plasma clot density and prolonged lysis times are associated with cardiovascular disease. In this study, we employed a functional proteomics approach to identify novel clot components which may influence clot phenotypes.
Analysis of perfused, solubilised plasma clots identified inflammatory proteins, including complement C3, as novel clot components. Analysis of paired plasma and serum samples confirmed concentration-dependent incorporation of C3 into clots. Surface plasmon resonance indicated high-affinity binding interactions between C3 and fibrinogen and fibrin. Turbidimetric clotting and lysis assays indicated C3 impaired fibrinolysis in a concentration-dependent manner, both in vitro and ex vivo.
These data indicate functional interactions between complement C3 and fibrin leading to prolonged fibrinolysis. These interactions are physiologically relevant in the context of protection following injury and suggest a mechanistic link between increased plasma C3 concentration and acute cardiovascular thrombotic events.
血浆凝块密度增加和溶解时间延长与心血管疾病相关。在这项研究中，我们采用了功能蛋白质组学方法来鉴定可能影响凝块表型的新型凝块成分。
对灌注、溶解的血浆凝块进行分析，鉴定出了炎症蛋白，包括补体 C3，作为新型凝块成分。对配对的血浆和血清样本的分析证实了 C3 浓度依赖性地掺入凝块。表面等离子体共振表明 C3 与纤维蛋白原和纤维蛋白之间存在高亲和力结合相互作用。浊度法凝血和溶解测定表明 C3 以浓度依赖性的方式在体外和体内均损害纤维蛋白溶解。
这些数据表明补体 C3 和纤维蛋白之间存在功能相互作用，导致纤维蛋白溶解延长。在损伤后的保护背景下，这些相互作用具有生理相关性，并提示血浆 C3 浓度升高与急性心血管血栓事件之间存在机制联系。
