Abstract
BackgroundWe have previously shown that many chronic, inflammatory diseases are accompanied, and possibly partly caused or exacerbated, by various coagulopathies, manifested as anomalous clots in the form of ‘dense matted deposits’. More recently, we have shown that these clots can be amyloid in nature, and that the plasma of healthy controls can be induced to form such clots by the addition of tiny amounts of bacterial lipopolysaccharide or lipoteichoic acid. Type 2 diabetes (T2D) is also accompanied by raised levels of LPS.MethodsWe use superresolution and confocal microscopies to investigate the amyloid nature of clots from healthy and T2D individuals.ResultsWe show here, with the established stain thioflavin T and the novel stains Amytracker™ 480 and 680, that the clotting of plasma from type 2 diabetics is also amyloid in nature, and that this may be prevented by the addition of suitable concentrations of LPS-binding protein.ConclusionThis implies strongly that there is indeed a microbial component to the development of type 2 diabetes, and suggests that LBP might be used as treatment for it and its sequelae.
Highlights
Inflammation is characterised by dysregulated circulating pro-inflammatory molecules, and such molecules have a pathological effect on the haematological system
Type 2 diabetes (T2D) plasma has aberrant fibrin(ogen) packaging, and this is associated with amyloid fibril formation, as demonstrated by the amyloid-selective stain thioflavin T (ThT) that binds to anomalous clots prepared by adding thrombin to diabetic plasma
Fluorescent markers and inflammagen binding agents We aimed to determine if the hypercoagulable clot structure that we have previously noted in T2D and confirmed by staining T2D platelet poor plasma (PPP) with thioflavin T (ThT), was amyloid in nature [59]
Summary
Inflammation is characterised by dysregulated circulating pro-inflammatory molecules, and such molecules have a pathological effect on the haematological system This is true of the immune cells, and of erythrocytes (RBCs), platelets and plasma proteins such as fibrin(ogen). The structure of the fibrin(ogen) protein changes, and this results in anomalous clot formation when fibrinogen is hydrolysed by thrombin [8,9,10,11]. Haematological pathology both reflects and is reflected by a. Type 2 diabetes (T2D) is accompanied by raised levels of LPS
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
