| Autor: |
Pretorius E; Department of Physiological Sciences, Stellenbosch University, Stellenbosch Private Bag X1 MATIELAND, 7602, Stellenbosch, South Africa. resiap@sun.ac.za., Mbotwe S; Department of Physiology, Faculty of Health Sciences, University of Pretoria, Arcadia, 0007, South Africa., Kell DB; School of Chemistry, The University of Manchester, 131 Princess St, MANCHESTER M1 7DN, Lancs, UK. dbk@manchester.ac.uk.; Manchester Institute of Biotechnology, The University of Manchester, 131 Princess St, MANCHESTER M1 7DN, Lancs, UK. dbk@manchester.ac.uk.; Centre for Synthetic Biology of Fine and Speciality Chemicals, The University of Manchester, 131 Princess St, MANCHESTER M1 7DN, Lancs, UK. dbk@manchester.ac.uk. |
| Abstrakt: |
Type 2 diabetes (T2D) has many cardiovascular complications, including a thrombotic propensity. Many such chronic, inflammatory diseases are accompanied (and may be exacerbated, and possibly even largely caused) by amyloid fibril formation. Recognising that there are few strong genetic associations underpinning T2D, but that amyloidogenesis of amylin is closely involved, we have been seeking to understand what might trigger the disease. Serum levels of bacterial lipopolysaccharide are raised in T2D, and we recently showed that fibrin(ogen) polymerisation during blood clotting can be affected strongly by LPS. The selectivity was indicated by the regularisation of clotting by lipopolysaccharide-binding protein (LBP). Since coagulopathies are a hallmark of T2D, we wondered whether they might too be caused by LPS (and reversed by LBP). We show here, using SEM and confocal microscopy, that platelet-poor-plasma from subjects with T2D had a much greater propensity for hypercoagulability and for amyloidogenesis, and that these could both be reversed by LBP. These data imply that coagulopathies are an important feature of T2D, and may be driven by 'hidden' LPS. Given the prevalence of amyloid formation in the sequelae of diabetes, this opens up novel strategies for both the prevention and treatment of T2D. |
