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Statins and C-reactive protein: in silico evidence on direct interaction

INTRODUCTION: Statins are known to lower CRP, and this reduction has been suggested to contribute to the established efficacy of these drugs in reducing cardiovascular events and outcomes. However, the exact mechanism underlying the CRP-lowering effect of statins remains elusive. METHODS: In order t...

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Autores principales: Shakour, Neda, Ruscica, Massimiliano, Hadizadeh, Farzin, Cirtori, Cesare, Banach, Maciej, Jamialahmadi, Tannaz, Sahebkar, Amirhossein
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Termedia Publishing House 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667423/
https://www.ncbi.nlm.nih.gov/pubmed/33224343
http://dx.doi.org/10.5114/aoms.2020.100304
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author Shakour, Neda
Ruscica, Massimiliano
Hadizadeh, Farzin
Cirtori, Cesare
Banach, Maciej
Jamialahmadi, Tannaz
Sahebkar, Amirhossein
author_facet Shakour, Neda
Ruscica, Massimiliano
Hadizadeh, Farzin
Cirtori, Cesare
Banach, Maciej
Jamialahmadi, Tannaz
Sahebkar, Amirhossein
author_sort Shakour, Neda
collection PubMed
description INTRODUCTION: Statins are known to lower CRP, and this reduction has been suggested to contribute to the established efficacy of these drugs in reducing cardiovascular events and outcomes. However, the exact mechanism underlying the CRP-lowering effect of statins remains elusive. METHODS: In order to test the possibility of direct interaction, we performed an in silico study by testing the orientation of the respective ligands (statins) and phosphorylcholine (the standard ligand of CRP) in the CRP active site using Molecular Operating Environment (MOE) software. RESULTS: Docking experiments showed that all statins could directly interact with CRP. Among statins, rosuvastatin had the strongest interaction with CRP (pKi = 16.14), followed by fluvastatin (pKi = 15.58), pitavastatin (pKi = 15.26), atorvastatin (pKi = 14.68), pravastatin (pKi = 13.95), simvastatin (pKi = 7.98) and lovastatin (pKi = 7.10). According to the above-mentioned results, rosuvastatin, fluvastatin, pitavastatin and atorvastatin were found to have stronger binding to CRP compared with the standard ligand phosphocholine (pKi = 14.55). CONCLUSIONS: This finding suggests a new mechanism of interaction between statins and CRP that could be independent of the putative cholesterol-lowering activity of statins.
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spelling pubmed-76674232020-11-20 Statins and C-reactive protein: in silico evidence on direct interaction Shakour, Neda Ruscica, Massimiliano Hadizadeh, Farzin Cirtori, Cesare Banach, Maciej Jamialahmadi, Tannaz Sahebkar, Amirhossein Arch Med Sci Letter INTRODUCTION: Statins are known to lower CRP, and this reduction has been suggested to contribute to the established efficacy of these drugs in reducing cardiovascular events and outcomes. However, the exact mechanism underlying the CRP-lowering effect of statins remains elusive. METHODS: In order to test the possibility of direct interaction, we performed an in silico study by testing the orientation of the respective ligands (statins) and phosphorylcholine (the standard ligand of CRP) in the CRP active site using Molecular Operating Environment (MOE) software. RESULTS: Docking experiments showed that all statins could directly interact with CRP. Among statins, rosuvastatin had the strongest interaction with CRP (pKi = 16.14), followed by fluvastatin (pKi = 15.58), pitavastatin (pKi = 15.26), atorvastatin (pKi = 14.68), pravastatin (pKi = 13.95), simvastatin (pKi = 7.98) and lovastatin (pKi = 7.10). According to the above-mentioned results, rosuvastatin, fluvastatin, pitavastatin and atorvastatin were found to have stronger binding to CRP compared with the standard ligand phosphocholine (pKi = 14.55). CONCLUSIONS: This finding suggests a new mechanism of interaction between statins and CRP that could be independent of the putative cholesterol-lowering activity of statins. Termedia Publishing House 2020-11-02 /pmc/articles/PMC7667423/ /pubmed/33224343 http://dx.doi.org/10.5114/aoms.2020.100304 Text en Copyright: © 2020 Termedia & Banach http://creativecommons.org/licenses/by-nc-sa/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
spellingShingle Letter
Shakour, Neda
Ruscica, Massimiliano
Hadizadeh, Farzin
Cirtori, Cesare
Banach, Maciej
Jamialahmadi, Tannaz
Sahebkar, Amirhossein
Statins and C-reactive protein: in silico evidence on direct interaction
title Statins and C-reactive protein: in silico evidence on direct interaction
title_full Statins and C-reactive protein: in silico evidence on direct interaction
title_fullStr Statins and C-reactive protein: in silico evidence on direct interaction
title_full_unstemmed Statins and C-reactive protein: in silico evidence on direct interaction
title_short Statins and C-reactive protein: in silico evidence on direct interaction
title_sort statins and c-reactive protein: in silico evidence on direct interaction
topic Letter
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667423/
https://www.ncbi.nlm.nih.gov/pubmed/33224343
http://dx.doi.org/10.5114/aoms.2020.100304
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