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

doi:10.5114/aoms.2020.100304

. 2020 Nov 2;16(6):1432-1439.

doi: 10.5114/aoms.2020.100304. eCollection 2020.

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

Neda Shakour¹, Massimiliano Ruscica², Farzin Hadizadeh³, Cesare Cirtori⁴, Maciej Banach^{5

6}, Tannaz Jamialahmadi^{7

8}, Amirhossein Sahebkar^{3

9

10}

Affiliations

¹ Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
² Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
³ Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
⁴ Centro Dislipidemie, A.S.S.T. Grande Ospedale Metropolitano Niguarda, Milan, Italy.
⁵ Department of Hypertension, WAM University Hospital, Medical University of Lodz, Lodz, Poland.
⁶ Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland.
⁷ Department of Food Science and Technology, Quchan Branch, Islamic Azad University, Quchan, Iran.
⁸ Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
⁹ Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
¹⁰ Halal Research Center of IRI, FDA, Tehran, Iran.

PMID: 33224343
PMCID: PMC7667423
DOI: 10.5114/aoms.2020.100304

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

Neda Shakour et al. Arch Med Sci. 2020.

. 2020 Nov 2;16(6):1432-1439.

doi: 10.5114/aoms.2020.100304. eCollection 2020.

Authors

Neda Shakour¹, Massimiliano Ruscica², Farzin Hadizadeh³, Cesare Cirtori⁴, Maciej Banach^{5

6}, Tannaz Jamialahmadi^{7

8}, Amirhossein Sahebkar^{3

9

10}

Affiliations

¹ Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
² Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
³ Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
⁴ Centro Dislipidemie, A.S.S.T. Grande Ospedale Metropolitano Niguarda, Milan, Italy.
⁵ Department of Hypertension, WAM University Hospital, Medical University of Lodz, Lodz, Poland.
⁶ Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland.
⁷ Department of Food Science and Technology, Quchan Branch, Islamic Azad University, Quchan, Iran.
⁸ Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
⁹ Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
¹⁰ Halal Research Center of IRI, FDA, Tehran, Iran.

PMID: 33224343
PMCID: PMC7667423
DOI: 10.5114/aoms.2020.100304

Abstract

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.

Keywords: C-reactive protein; docking; inflammation; interaction; statins.

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Conflict of interest statement

The authors declare no conflict of interest.

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References

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[1] Otterness IG. The value of C-reactive protein measurement in rheumatoid arthritis. Semin Arthritis Rheum. 1994;24:91–104. - PubMed

[2] Otterness IG. The value of C-reactive protein measurement in rheumatoid arthritis. Semin Arthritis Rheum. 1994;24:91–104. - PubMed

[3] Stumpf C, Sheriff A, Zimmermann S, et al. C-reactive protein levels predict systolic heart failure and outcome in patients with first ST-elevation myocardial infarction treated with coronary angioplasty. Arch Med Sci. 2017;13:1086–93. - PMC - PubMed

[4] Stumpf C, Sheriff A, Zimmermann S, et al. C-reactive protein levels predict systolic heart failure and outcome in patients with first ST-elevation myocardial infarction treated with coronary angioplasty. Arch Med Sci. 2017;13:1086–93. - PMC - PubMed

[5] Ticinesi A, Lauretani F, Nouvenne A, et al. C-reactive protein (CRP) measurement in geriatric patients hospitalized for acute infection. Eur J Intern Med. 2017;37:7–12. - PubMed

[6] Ticinesi A, Lauretani F, Nouvenne A, et al. C-reactive protein (CRP) measurement in geriatric patients hospitalized for acute infection. Eur J Intern Med. 2017;37:7–12. - PubMed

[7] Shadick NA, Cook NR, Karlson EW, et al. C-reactive protein in the prediction of rheumatoid arthritis in women. Arch Intern Med. 2006;166:2490–4. - PubMed

[8] Shadick NA, Cook NR, Karlson EW, et al. C-reactive protein in the prediction of rheumatoid arthritis in women. Arch Intern Med. 2006;166:2490–4. - PubMed

[9] Tsimikas S, Willerson JT, Ridker PM. C-reactive protein and other emerging blood biomarkers to optimize risk stratification of vulnerable patients. J Am Coll Cardiol. 2006;47:C19–31. - PubMed

[10] Tsimikas S, Willerson JT, Ridker PM. C-reactive protein and other emerging blood biomarkers to optimize risk stratification of vulnerable patients. J Am Coll Cardiol. 2006;47:C19–31. - PubMed

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

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

Authors

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Abstract

Conflict of interest statement

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