Gingipain R1 and lipopolysaccharide from Porphyromonas gingivalis have major effects on blood clot morphology and mechanics

Abstract

Background: Porphyromonas gingivalis and its inflammagens is associated with a number of systemic diseases, such as cardiovascular disease and type 2 diabetes (T2DM). The proteases, gingipains have also recently been identified in brains of Alzheimer’s disease patients and in blood of Parkinson’s disease patients. Bacterial inflammagens, including lipopolysaccharides (LPSs) and various proteases in circulation may drive systemic inflammation. Methods: Here, we investigate the effects of the bacterial products LPS from Escherichia coli and Porphyromonas gingivalis, and also the P. gingivalis gingipain (recombinant P. gingivalis gingipain R1 (RgpA)), on clot architecture and clot formation in whole blood and plasma from healthy individuals, as well as in purified fibrinogen models. Structural analysis of clots was performed using confocal, scanning electron microscopy and AFM-Raman. We use thromboelastography (TEG) and rheometry to compare the static and dynamic mechanical properties of clots. Results: We found that these inflammagens may interact with fibrin(ogen) and this interaction causes anomalous blood clotting. Conclusions: These techniques, in combination provide insight into the effects of these bacterial products on cardiovascular health, and particularly clot structure and mechanics.

Relative Hypercoagulopathy of the SARS-CoV-2 Beta and Delta Variants when Compared to the Less Severe Omicron Variants Is Related to TEG Parameters, the Extent of Fibrin Amyloid Microclots, and the Severity of Clinical Illness

“…27 Our group has previously shown amyloid fibrin deposits in numerous inflammatory conditions. 46 47 48 49 50 51 52 53 However, the extent of the microclot presence in both acute COVID-19 and long COVID was found to be significantly more than in other chronic systemic inflammatory conditions. 32 36…”

Early management of severe COVID-19 coagulopathy should be guided by TEG®, microclot and platelet mapping

“…These fluorescence markers are typically used to show amyloid changes to proteins [31,56,[76][77][78], suggesting the misfolding seen in fibrin(ogen) during the presence of inflammagens in the blood, could also be described as amyloid. We showed, that when fibrin(ogen) is exposed to increased levels of inflammatory biomarkers and bacterial (viral) inflammagens, either in the laboratory or in patients with increased levels, TEG ® of PPP was significantly hypercoagulable [76][77][78][79]. Figure 3A shows the uncoiling of the fibrin(ogen) molecule where it caused plasma and WB to become hypercoagulable.…”

Low levels of salivary lactoferrin may affect oral dysbiosis and contribute to Alzheimer’s disease: A hypothesis

“…This could facilitate proliferation of some of the most virulent bacteria in periodontal infections, and possibly promote AD by systemic spread of these bacteria and their inflammagens to the brain. Inflammagens from P. gingivalis such as gingipain R1 (RgpA) and LPS have been reported to have major effects on blood clot morphology and mechanics thereby driving systemic inflammation [33]. Interestingly, intake of tablets containing LF (60 mg/d) and lactoperoxidase (7.8 mg/d) improved gingival inflammation and oral health-related quality of life in healthy adults [34] supporting the concept that low levels of LF are indicators of dysbiosis.…”