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Being Eaten Alive: How Energy-Deprived Cells Are Disposed of, Mediated by C-Reactive Protein—Including a Treatment Option

In medicine, C-reactive protein (CRP) has become established primarily as a biomarker, predicting patient prognosis in many indications. Recently, however, there has been mounting evidence that it causes inflammatory injury. As early as 1999, CRP was shown to induce cell death after acute myocardial...

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Detalles Bibliográficos
Autores principales: Sheriff, Ahmed, Kunze, Rudolf, Brunner, Patrizia, Vogt, Birgit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10452736/
https://www.ncbi.nlm.nih.gov/pubmed/37626775
http://dx.doi.org/10.3390/biomedicines11082279
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author Sheriff, Ahmed
Kunze, Rudolf
Brunner, Patrizia
Vogt, Birgit
author_facet Sheriff, Ahmed
Kunze, Rudolf
Brunner, Patrizia
Vogt, Birgit
author_sort Sheriff, Ahmed
collection PubMed
description In medicine, C-reactive protein (CRP) has become established primarily as a biomarker, predicting patient prognosis in many indications. Recently, however, there has been mounting evidence that it causes inflammatory injury. As early as 1999, CRP was shown to induce cell death after acute myocardial infarction (AMI) in rats and this was found to be dependent on complement. The pathological effect of CRP was subsequently confirmed in further animal species such as rabbit, mouse and pig. A conceptual gap was recently closed when it was demonstrated that ischemia in AMI or ischemia/hypoxia in the severe course of COVID-19 causes a drastic lack of energy in involved cells, resulting in an apoptotic presentation because these cells cannot repair/flip-flop altered lipids. The deprivation of energy leads to extensive expression on the cell membranes of the CRP ligand lysophosphatidylcholine. Upon attachment of CRP to this ligand, the classical complement pathway is triggered leading to the swift elimination of viable cells with the appearance of an apoptotic cell by phagocytes. They are being eaten alive. This, consequently, results in substantial fibrotic remodeling within the involved tissue. Inhibiting this pathomechanism via CRP-targeting therapy has been shown to be beneficial in different indications.
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spelling pubmed-104527362023-08-26 Being Eaten Alive: How Energy-Deprived Cells Are Disposed of, Mediated by C-Reactive Protein—Including a Treatment Option Sheriff, Ahmed Kunze, Rudolf Brunner, Patrizia Vogt, Birgit Biomedicines Perspective In medicine, C-reactive protein (CRP) has become established primarily as a biomarker, predicting patient prognosis in many indications. Recently, however, there has been mounting evidence that it causes inflammatory injury. As early as 1999, CRP was shown to induce cell death after acute myocardial infarction (AMI) in rats and this was found to be dependent on complement. The pathological effect of CRP was subsequently confirmed in further animal species such as rabbit, mouse and pig. A conceptual gap was recently closed when it was demonstrated that ischemia in AMI or ischemia/hypoxia in the severe course of COVID-19 causes a drastic lack of energy in involved cells, resulting in an apoptotic presentation because these cells cannot repair/flip-flop altered lipids. The deprivation of energy leads to extensive expression on the cell membranes of the CRP ligand lysophosphatidylcholine. Upon attachment of CRP to this ligand, the classical complement pathway is triggered leading to the swift elimination of viable cells with the appearance of an apoptotic cell by phagocytes. They are being eaten alive. This, consequently, results in substantial fibrotic remodeling within the involved tissue. Inhibiting this pathomechanism via CRP-targeting therapy has been shown to be beneficial in different indications. MDPI 2023-08-16 /pmc/articles/PMC10452736/ /pubmed/37626775 http://dx.doi.org/10.3390/biomedicines11082279 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Perspective
Sheriff, Ahmed
Kunze, Rudolf
Brunner, Patrizia
Vogt, Birgit
Being Eaten Alive: How Energy-Deprived Cells Are Disposed of, Mediated by C-Reactive Protein—Including a Treatment Option
title Being Eaten Alive: How Energy-Deprived Cells Are Disposed of, Mediated by C-Reactive Protein—Including a Treatment Option
title_full Being Eaten Alive: How Energy-Deprived Cells Are Disposed of, Mediated by C-Reactive Protein—Including a Treatment Option
title_fullStr Being Eaten Alive: How Energy-Deprived Cells Are Disposed of, Mediated by C-Reactive Protein—Including a Treatment Option
title_full_unstemmed Being Eaten Alive: How Energy-Deprived Cells Are Disposed of, Mediated by C-Reactive Protein—Including a Treatment Option
title_short Being Eaten Alive: How Energy-Deprived Cells Are Disposed of, Mediated by C-Reactive Protein—Including a Treatment Option
title_sort being eaten alive: how energy-deprived cells are disposed of, mediated by c-reactive protein—including a treatment option
topic Perspective
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10452736/
https://www.ncbi.nlm.nih.gov/pubmed/37626775
http://dx.doi.org/10.3390/biomedicines11082279
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