Diabetologia (2012) 55:1103–1113 DOI 10.1007/s00125-011-2301-7
ARTICLE
A novel mechanism for hypofibrinolysis in diabetes: the role of complement C3 K. Hess & S. H. Alzahrani & M. Mathai & V. Schroeder & A. M. Carter & G. Howell & T. Koko & M. W. J. Strachan & J. F. Price & K. A. Smith & P. J. Grant & R. A. Ajjan
Received: 20 May 2011 / Accepted: 12 August 2011 / Published online: 15 September 2011 # Springer-Verlag 2011
Abstract Aims/hypothesis Impaired fibrin clot lysis is a key abnormality in diabetes and complement C3 is one protein identified in blood clots. This work investigates the mechanistic pathways linking C3 and hypofibrinolysis in diabetes using ex vivo/in vitro studies. Methods Fibrinolysis and C3 plasma levels were determined in type 1 diabetic patients and healthy controls, and the effects of glycaemia investigated. C3 incorporation into fibrin clots and modulation of fibrinolysis were analysed by K. Hess : S. H. Alzahrani : V. Schroeder : A. M. Carter : T. Koko : K. A. Smith : P. J. Grant : R. A. Ajjan (*) Division of Cardiovascular and Diabetes Research, Multidisciplinary Cardiovascular Research Centre, Leeds Institute for Genetics, Health and Therapeutics, LIGHT Laboratories, Clarendon Way, University of Leeds, Leeds LS2 9JT, UK e-mail:
[email protected] K. Hess Department of Internal Medicine I, University Hospital RWTH Aachen, Aachen, Germany M. Mathai Department of Paediatrics, Bradford Royal Infirmary, Bradford, UK G. Howell Faculty of Biological Sciences, University of Leeds, Leeds, UK M. W. J. Strachan Metabolic Unit, Western General Hospital, Edinburgh, UK J. F. Price Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK
ELISA, immunoblotting, turbidimetric assays and electron and confocal microscopy. Results Clot lysis time was longer in diabetic children than in controls (599±18 and 516±12 s respectively; p