Hypofibrinolysis in type 2 diabetes: the role of the inflammatory pathway and complement C3
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- 作者：Katharina Hess (1)
Saad H. Alzahrani (2) (3)
Jackie F. Price (4)
Mark W. Strachan (5)
Natalie Oxley (2)
Rhodri King (2)
Tobias Gamlen (2)
Verena Schroeder (6)
Paul D. Baxter (7)
Ramzi A. Ajjan (2) - 关键词：Complement C3 ; C ; reactive protein ; CRP ; Diabetes ; Fibrinolysis
- 刊名：Diabetologia
- 出版年：2014
- 出版时间：August 2014
- 年：2014
- 卷：57
- 期：8
- 页码：1737-1741
- 全文大小：154 KB
- 参考文献：1. Alzahrani SH, Ajjan RA (2010) Coagulation and fibrinolysis in diabetes. Diabetes Vasc Dis Res 7:260-73 CrossRef
2. Hess K, Alzahrani S, Mathai M et al (2012) A novel mechanism for hypofibrinolysis in diabetes: the role of complement C3. Diabetologia 55:1103-113 CrossRef
3. Alzahrani SH, Hess K, Price JF et al (2012) Gender-specific alterations in fibrin structure function in type 2 diabetes: associations with cardiometabolic and vascular markers. J Clin Endocrinol Metab 97:E2282–E2287 CrossRef
4. Schroeder V, Carter AM, Dunne J, Mansfield MW, Grant PJ (2010) Proinflammatory and hypofibrinolytic phenotype in healthy first-degree relatives of patients with type 2 diabetes. J Thromb Haemost 8:2080-082 CrossRef
5. Price JF, Reynolds RM, Mitchell RJ et al (2008) The Edinburgh type 2 diabetes study: study protocol. BMC Endocr Disord 8:18 CrossRef
6. Yasojima K, Schwab C, McGeer EG, McGeer PL (2001) Complement components, but not complement inhibitors, are upregulated in atherosclerotic plaques. Arterioscler Thromb Vasc Biol 21:1214-219 CrossRef
7. Széplaki G, Prohászka Z, Duba J et al (2004) Association of high serum concentration of the third component of complement (C3) with pre-existing severe coronary artery disease and new vascular events in women. Atherosclerosis 177:383-89 CrossRef
8. Wei JN, Li HY, Sung FC et al (2012) Obesity and clustering of cardiovascular disease risk factors are associated with elevated plasma complement C3 in children and adolescents. Pediatr Diabetes 13:476-83 CrossRef
9. Amara U, Flierl MA, Rittirsch D et al (2010) Molecular intercommunication between the complement and coagulation systems. J Immunol 185:5628-636 CrossRef - 作者单位：Katharina Hess (1)
Saad H. Alzahrani (2) (3)
Jackie F. Price (4)
Mark W. Strachan (5)
Natalie Oxley (2)
Rhodri King (2)
Tobias Gamlen (2)
Verena Schroeder (6)
Paul D. Baxter (7)
Ramzi A. Ajjan (2)
1. Department of Cardiology, University Hospital RWTH Aachen, Aachen, Germany
2. Division of Cardiovascular and Diabetes Research, Leeds Institute for Genetics, Health and Therapeutics, LIGHT Laboratories, Clarendon Way, University of Leeds, Leeds, LS2 9JT, UK
3. Specialized Diabetes and Endocrine Centre, King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia
4. Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK
5. Metabolic Unit, Western General Hospital, Edinburgh, UK
6. University Clinic of Hematology and Central Hematology Laboratory, Hemostasis Research Laboratory, University Hospital and University of Bern, Bern, Switzerland
7. Division of Epidemiology and Biostatistics, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, UK - ISSN：1432-0428
文摘
Aims/hypothesis Plasminogen activator inhibitor-1 (PAI-1) has been regarded as the main antifibrinolytic protein in diabetes, but recent work indicates that complement C3 (C3), an inflammatory protein, directly compromises fibrinolysis in type 1 diabetes. The aim of the current project was to investigate associations between C3 and fibrinolysis in a large cohort of individuals with type 2 diabetes. Methods Plasma levels of C3, C-reactive protein (CRP), PAI-1 and fibrinogen were analysed by ELISA in 837 patients enrolled in the Edinburgh Type 2 Diabetes Study. Fibrin clot lysis was analysed using a validated turbidimetric assay. Results Clot lysis time correlated with C3 and PAI-1 plasma levels (r--.24, p--.001 and r--.22, p--.001, respectively). In a multivariable regression model involving age, sex, BMI, C3, PAI-1, CRP and fibrinogen, and using log-transformed data as appropriate, C3 was associated with clot lysis time (regression coefficient 0.227 [95% CI 0.161, 0.292], p--.001), as was PAI-1 (regression coefficient 0.033 [95% CI 0.020, 0.064], p--.05) but not fibrinogen (regression coefficient 0.003 [95% CI ?.046, 0.051], p--.92) or CRP (regression coefficient 0.024 [95% CI ?.008, 0.056], p--.14). No correlation was demonstrated between plasma levels of C3 and PAI-1 (r-??0.03, p--.44), consistent with previous observations that the two proteins affect different pathways in the fibrinolytic system. Conclusions/interpretation Similarly to PAI-1, C3 plasma levels are independently associated with fibrin clot lysis in individuals with type 2 diabetes. Therefore, future studies should analyse C3 plasma levels as a surrogate marker of fibrinolysis potential in this population.