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      DYNAMICS OF CHANGES OF C-REACTIVE PROTEIN LEVEL IN BLOOD SERUM IN THE DEVELOPMENT AND COURSE OF EXPERIMENTAL PERIODONTITIS AND THEIR CORRECTION BY FLAVONOL

      1 , 1 , 2 , 1 , 2
      Wiadomości Lekarskie
      ALUNA

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          Abstract

          The aim: To study the value of C-reactive protein in the experimental animals blood serum with bacterial-immune periodontitis and its correction with quercetin. Materials and methods: Modeling of periodontitis was performed by the following method: after thiopental anesthesia (at a dose of 40 mg / kg intramuscularly) rats were fixed. A subcostal injection of 0.01 ml of egg protein with cultures of Streptococcus hemolytic and Staphylococcus aureus at a dose of 4 CFU was performed in the area of periodontal tissues of the lower incisor as an initiating inflammatory factor. To enhance the immune process, a complete Freund’s adjuvant was introduced into the animal’s hind limb at the same time. Results: Analysis of the results of the study of the content of C-reactive protein in the blood serum of animals with experimental bacteria and immune periodontitis, receiving injections of quercetin, showed a significant decrease by 1.31 times, compared with animals with this simulated pathology on the 14th day of the experiment without the use of flavonol. When comparing this indicator on the 14th day of development of experimental periodontitis with correction, it was found that it remained slightly higher than the indicators of the intact group of rats. Conclusions: The level of C-reactive protein in the blood serum of experimental animals is an important indicator of the immune-inflammatory response, which increases its activation of the inflammatory system. The administration of flavonoid quercetin for 7 days helps to reduce the level of C-reactive protein in the blood serum of animals with experimental bacterial and immune periodontitis.

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          From C-Reactive Protein to Interleukin-6 to Interleukin-1: Moving Upstream To Identify Novel Targets for Atheroprotection.

          Plasma levels of the inflammatory biomarker high-sensitivity C-reactive protein (hsCRP) predict vascular risk with an effect estimate as large as that of total or high-density lipoprotein cholesterol. Further, randomized trial data addressing hsCRP have been central to understanding the anti-inflammatory effects of statin therapy and have consistently demonstrated on-treatment hsCRP levels to be as powerful a predictor of residual cardiovascular risk as on-treatment levels of low-density lipoprotein cholesterol. Yet, although hsCRP is clinically useful as a biomarker for risk prediction, most mechanistic studies suggest that CRP itself is unlikely to be a target for intervention. Moving upstream in the inflammatory cascade from CRP to interleukin (IL)-6 to IL-1 provides novel therapeutic opportunities for atheroprotection that focus on the central IL-6 signaling system and ultimately on inhibition of the IL-1β-producing NOD-like receptor family pyrin domain containing 3 inflammasome. Cholesterol crystals, neutrophil extracellular traps, atheroprone flow, and local tissue hypoxia activate the NOD-like receptor family pyrin domain containing 3 inflammasome. As such, a unifying concept of hsCRP as a downstream surrogate biomarker for upstream IL-1β activity has emerged. From a therapeutic perspective, small ischemia studies show reductions in acute-phase hsCRP production with the IL-1 receptor antagonist anakinra and the IL-6 receptor blocker tocilizumab. A phase IIb study conducted among diabetic patients at high vascular risk indicates that canakinumab, a human monoclonal antibody that targets IL-1β, markedly reduces plasma levels of IL-6, hsCRP, and fibrinogen with little change in atherogenic lipids. Canakinumab in now being tested as a method to prevent recurrent cardiovascular events in a randomized trial of 10 065 post-myocardial infarction patients with elevated hsCRP that is fully enrolled and due to complete in 2017. Clinical trials using alternative anti-inflammatory agents active against the CRP/IL-6/IL-1 axis, including low-dose methotrexate and colchicine, are being explored. If successful, these trials will close the loop on the inflammatory hypothesis of atherosclerosis and serve as examples of how fundamental biologic principles can be translated into personalized medical practice.
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            C-Reactive Protein in Atherothrombosis and Angiogenesis

            C-reactive protein (CRP) is a short pentraxin mainly found as a pentamer in the circulation, or as non-soluble monomers CRP (mCRP) in tissues, exerting different functions. This review is focused on discussing the role of CRP in cardiovascular disease, including recent advances on the implication of CRP and its forms specifically on the pathogenesis of atherothrombosis and angiogenesis. Besides its role in the humoral innate immune response, CRP contributes to cardiovascular disease progression by recognizing and binding multiple intrinsic ligands. mCRP is not present in the healthy vessel wall but it becomes detectable in the early stages of atherogenesis and accumulates during the progression of atherosclerosis. CRP inhibits endothelial nitric oxide production and contributes to plaque instability by increasing endothelial cell adhesion molecules expression, by promoting monocyte recruitment into the atheromatous plaque and by enzymatically binding to modified low-density lipoprotein. CRP also contributes to thrombosis, but depending on its form it elicits different actions. Pentameric CRP has no involvement in thrombogenesis, whereas mCRP induces platelet activation and thrombus growth. In addition, mCRP has apparently contradictory pro-angiogenic and anti-angiogenic effects determining tissue remodeling in the atherosclerotic plaque and in infarcted tissues. Overall, CRP contributes to cardiovascular disease by several mechanisms that deserve an in-depth analysis.
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              C-reactive protein can upregulate VEGF expression to promote ADSC-induced angiogenesis by activating HIF-1α via CD64/PI3k/Akt and MAPK/ERK signaling pathways

              Background Proliferation of the vasa vasorum has been implicated in the pathogenesis of atherosclerosis, and the vasa vasorum is closely associated with resident stem cells within the vasculature. C-reactive protein (CRP) is positively correlated with cardiovascular disease risk, and our previous study demonstrated that it induces inflammatory reactions of perivascular adipose tissue by targeting adipocytes. Methods Here we investigated whether CRP affected the proliferation and proangiogenic paracrine activity of adipose-derived stem cells (ADSCs), which may contribute to vasa vasorum angiogenesis. Results We found that CRP did not affect ADSC apoptosis, cell cycle, or proliferation but did increase their migration by activating the PI3K/Akt pathway. Our results demonstrated that CRP can upregulate vascular endothelial growth factor-A (VEGF-A) expression by activating hypoxia inducible factor-1α (HIF-1α) in ADSCs, which significantly increased tube formation on Matrigel and functional vessels in the Matrigel plug angiogenesis assay. The inhibition of CRP-activated phosphorylation of ERK and Akt can suppress CRP-stimulated HIF-1α activation and VEGF-A expression. CRP can also stimulate proteolytic activity of matrix metalloproteinase-2 in ADSCs. Furthermore, CRP binds activating CD64 on ADSCs, rather than CD16/32. Conclusion Our findings implicate that CRP might play a role in vasa vasorum growth by activating the proangiogenic activity of ADSCs. Electronic supplementary material The online version of this article (doi:10.1186/s13287-016-0377-1) contains supplementary material, which is available to authorized users.
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                Author and article information

                Journal
                Wiadomości Lekarskie
                Wiad Lek
                ALUNA
                00435147
                2022
                February 2022
                2022
                February 2022
                : 75
                : 2
                : 451-455
                Affiliations
                [1 ]I. HORBACHEVSKY TERNOPIL NATIONAL MEDICAL UNIVERSITY, TERNOPIL, UKRAINE
                [2 ]POLTAVA STATE MEDICAL UNIVERSITY, POLTAVA, UKRAINE
                Article
                10.36740/WLek202202122
                35307675
                45bcee4a-bf72-4777-b5df-674b099c1e90
                © 2022
                History

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