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      The thrombotic potential of oral pathogens

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          Abstract

          In recent times the concept of infectious agents playing a role in cardiovascular disease has attracted much attention. Chronic oral disease such as periodontitis, provides a plausible route for entry of bacteria to the circulation. Upon entry to the circulation, the oral bacteria interact with platelets. It has been proposed that their ability to induce platelet aggregation and support platelet adhesion is a critical step in the pathogenesis of the infection process. Many published studies have demonstrated multiple mechanisms through which oral bacteria are able to bind to and activate platelets. This paper will review the various mechanisms oral bacteria use to interact with platelets.

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          The interaction of bacterial pathogens with platelets.

          In recent years, the frequency of serious cardiovascular infections such as endocarditis has increased, particularly in association with nosocomially acquired antibiotic-resistant pathogens. Growing evidence suggests a crucial role for the interaction of bacteria with human platelets in the pathogenesis of cardiovascular infections. Here, we review the nature of the interactions between platelets and bacteria, and the role of these interactions in the pathogenesis of endocarditis and other cardiovascular diseases.
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            Inflammation and infections as risk factors for ischemic stroke.

            Inflammatory processes have fundamental roles in stroke in both the etiology of ischemic cerebrovascular disease and the pathophysiology of cerebral ischemia. We summarize clinical data on infection and inflammation as risk or trigger factors for human stroke and investigate current evidence for the hypothesis of a functional interrelation between traditional risk factors, genetic predisposition, and infection/inflammation in stroke pathogenesis. Several traditional vascular risk factors are associated with proinflammatory alterations, including leukocyte activation, and predispose cerebral vasculature to thrombogenesis on inflammatory stimulation. Furthermore, accumulation of inflammatory cells, mainly monocytes/macrophages, within the vascular wall starts early during atherogenesis. During later disease stages, their activation can lead to plaque rupture and thrombus formation, increasing stroke risk. Inflammatory markers (eg, leukocytes, fibrinogen, C-reactive protein) are independent predictors of ischemic stroke. Chronic infections (eg, infection with Chlamydia pneumoniae or Helicobacter pylori) were found to increase the risk of stroke; however, study results are at variance, residual confounding is not excluded, and causality is not established at present. In case-control studies, acute infection within the preceding week was a trigger factor for ischemic stroke. Acute and exacerbating chronic infection may act by activating coagulation and chronic infections and may contribute to atherogenesis. Genetic predisposition of the inflammatory host response may be an important codeterminant for atherogenesis and stroke risk. Inflammation contributes to stroke risk via various interrelated mechanisms. Infectious diseases, traditional risk factors, and genetic susceptibility may cooperate in stimulating inflammatory pathways. Final proof of a causal role of infectious/inflammatory mechanisms in stroke pathogenesis is still lacking and will require interventional studies.
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              Specific synergy of multiple substrate-receptor interactions in platelet thrombus formation under flow.

              We have used confocal videomicroscopy in real time to delineate the adhesive interactions supporting platelet thrombus formation on biologically relevant surfaces. Type I collagen fibrils exposed to flowing blood adsorb von Willebrand factor (vWF), to which platelets become initially tethered with continuous surface translocation mediated by the membrane glycoprotein Ib alpha. This step is essential at high wall shear rates to allow subsequent irreversible adhesion and thrombus growth mediated by the integrins alpha2beta1 and alpha(IIb)beta3. On subendothelial matrix, endogenous vWF and adsorbed plasma vWF synergistically initiate platelet recruitment, and alpha2beta1 remains key along with alpha(IIb)beta3 for normal thrombus development at all but low shear rates. Thus, hemodynamic forces and substrate characteristics define the platelet adhesion pathways leading to thrombogenesis.
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                Author and article information

                Journal
                J Oral Microbiol
                JOM
                Journal of Oral Microbiology
                CoAction Publishing
                2000-2297
                26 August 2009
                2009
                : 1
                : 10.3402/jom.v1i0.1999
                Affiliations
                [1 ]Cardiovascular Infection Group, School of Pharmacy, Royal College of Surgeons in Ireland, Dublin 2, Ireland
                [2 ]Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin 2, Ireland
                Author notes
                [* ] Steven W. Kerrigan, Cardiovascular Infection Group, School of Pharmacy & Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin 2, Ireland. Tel: +353 1 402 2104. Fax: +353 1 402 2453. Email: skerrigan@ 123456rcsi.ie
                Article
                JOM-1-1999
                10.3402/jom.v1i0.1999
                3077004
                21523210
                86ad6d44-895c-474b-a067-44ff0a00adb9
                © 2009 Steven W. Kerrigan and Dermot Cox

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 3.0 Unported License, permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 May 2009
                : 26 July 2009
                : 30 July 2009
                Categories
                Review Article

                Microbiology & Virology
                thrombosis,oral pathogens,cardiovascular disease,virulence,streptococci,platelets,bacteria

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