CRP Is Transported by Monocytes and Monocyte-Derived Exosomes in the Blood of Patients with Coronary Artery Disease

Overview

Journal Biomedicines

Specialty Biomedical Engineering

Date 2020 Oct 22

PMID 33086769

Citations 12

Authors

Ivan Melnikov

Sergey Kozlov

Olga Saburova

Ekaterina Zubkova

Olga Guseva

Sergey Domogatsky

Tatiana Arefieva

Natalia Radyukhina

Maria Zvereva

Yuliya Avtaeva

Lyudmila Buryachkovskaya

Zufar Gabbasov

Affiliations

Soon will be listed here.

Abstract

The objective of this work was to study the ability of blood cells and their microparticles to transport monomeric and pentameric forms of C-reactive protein (mCRP and pCRP) in the blood of patients with coronary artery disease (CAD). Blood was obtained from 14 patients with CAD 46 ± 13 years old and 8 healthy volunteers 49 ± 13.6 years old. Blood cells and microparticles with mCRP and pCRP on their surface were detected by flow cytometry. Messenger RNA (mRNA) of CRP was extracted from peripheral blood monocytes stimulated with lipopolysaccharide (LPS) and granulocyte-macrophage colony-stimulating factor (GM-CSF). mRNA of CRP in monocytes was detected with PCR. Monocytes were predominantly pCRP-positive (92.9 ± 6.8%). mCRP was present on 22.0 ± 9.6% of monocyte-derived exosomes. mCRP-positive leukocyte-derived microparticle counts were significantly higher (8764 ± 2876/µL) in the blood of patients with CAD than in healthy volunteers (1472 ± 307/µL). LPS and GM-CSF stimulated monocytes expressed CRP mRNA transcripts levels (0.79 ± 0.73-fold), slightly lower relative to unstimulated hepatocytes of the HepG2 cell line (1.0 ± 0.6-fold), but still detectable. The ability of monocytes to transport pCRP in blood flow, and monocyte-derived exosomes to transmit mCRP, may contribute to the maintenance of chronic inflammation in CAD.

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References

Kolb-Bachofen V, Egenhofer C . Expression of membrane-associated C-reactive protein by human monocytes: indications for a selectin-like activity participating in adhesion. Glycoconj J. 1995; 12(2):122-7. DOI: 10.1007/BF00731355. View

Slevin M, Krupinski J . A role for monomeric C-reactive protein in regulation of angiogenesis, endothelial cell inflammation and thrombus formation in cardiovascular/cerebrovascular disease?. Histol Histopathol. 2009; 24(11):1473-8. DOI: 10.14670/HH-24.1473. View

Sadallah S, Eken C, Schifferli J . Ectosomes as immunomodulators. Semin Immunopathol. 2010; 33(5):487-95. DOI: 10.1007/s00281-010-0232-x. View

Pepys M, Hirschfield G, Tennent G, Gallimore J, Kahan M, Bellotti V . Targeting C-reactive protein for the treatment of cardiovascular disease. Nature. 2006; 440(7088):1217-21. DOI: 10.1038/nature04672. View

Ruf J, Vairo D, Paganelli F, Guieu R . Extracellular vesicles with ubiquitinated adenosine A receptor in plasma of patients with coronary artery disease. J Cell Mol Med. 2019; 23(10):6805-6811. PMC: 6787504. DOI: 10.1111/jcmm.14564. View

Kiefer C, Stock R, Flanagan S, Darling C, Smith C, Snyder L . Early verification of myocardial ischemia with a novel biomarker of acute tissue damage: C-reactive protein fractional forms. Clin Chim Acta. 2012; 413(19-20):1536-41. DOI: 10.1016/j.cca.2012.06.023. View

Crawford J, Trial J, Nambi V, Hoogeveen R, Taffet G, Entman M . Plasma Levels of Endothelial Microparticles Bearing Monomeric C-reactive Protein are Increased in Peripheral Artery Disease. J Cardiovasc Transl Res. 2016; 9(3):184-193. PMC: 4874871. DOI: 10.1007/s12265-016-9678-0. View

Azevedo L, Janiszewski M, Pontieri V, Pedro M, Bassi E, Tucci P . Platelet-derived exosomes from septic shock patients induce myocardial dysfunction. Crit Care. 2007; 11(6):R120. PMC: 2246209. DOI: 10.1186/cc6176. View

Molins B, Pena E, Vilahur G, Mendieta C, Slevin M, Badimon L . C-reactive protein isoforms differ in their effects on thrombus growth. Arterioscler Thromb Vasc Biol. 2008; 28(12):2239-46. DOI: 10.1161/ATVBAHA.108.174359. View

10.

Ji S, Ma L, Bai C, Shi J, Li H, Potempa L . Monomeric C-reactive protein activates endothelial cells via interaction with lipid raft microdomains. FASEB J. 2009; 23(6):1806-16. DOI: 10.1096/fj.08-116962. View

11.

Paganelli F, Gaudry M, Ruf J, Guieu R . Recent advances in the role of the adenosinergic system in coronary artery disease. Cardiovasc Res. 2020; 117(5):1284-1294. DOI: 10.1093/cvr/cvaa275. View

12.

Ciubotaru I, Potempa L, Wander R . Production of modified C-reactive protein in U937-derived macrophages. Exp Biol Med (Maywood). 2005; 230(10):762-70. DOI: 10.1177/153537020523001010. View

13.

Haider D, Leuchten N, Schaller G, Gouya G, Kolodjaschna J, Schmetterer L . C-reactive protein is expressed and secreted by peripheral blood mononuclear cells. Clin Exp Immunol. 2006; 146(3):533-9. PMC: 1810406. DOI: 10.1111/j.1365-2249.2006.03224.x. View

14.

Ling Z, Combes V, Grau G, King N . Microparticles as immune regulators in infectious disease - an opinion. Front Immunol. 2012; 2:67. PMC: 3342294. DOI: 10.3389/fimmu.2011.00067. View

15.

Eisenhardt S, Thiele J, Bannasch H, Stark G, Peter K . C-reactive protein: how conformational changes influence inflammatory properties. Cell Cycle. 2009; 8(23):3885-92. DOI: 10.4161/cc.8.23.10068. View

16.

Ji S, Wu Y, Zhu L, Potempa L, Sheng F, Lu W . Cell membranes and liposomes dissociate C-reactive protein (CRP) to form a new, biologically active structural intermediate: mCRP(m). FASEB J. 2006; 21(1):284-94. DOI: 10.1096/fj.06-6722com. View

17.

Wang J, Tang B, Liu X, Wu X, Wang H, Xu D . Increased monomeric CRP levels in acute myocardial infarction: a possible new and specific biomarker for diagnosis and severity assessment of disease. Atherosclerosis. 2015; 239(2):343-9. DOI: 10.1016/j.atherosclerosis.2015.01.024. View

18.

Khreiss T, Jozsef L, Potempa L, Filep J . Loss of pentameric symmetry in C-reactive protein induces interleukin-8 secretion through peroxynitrite signaling in human neutrophils. Circ Res. 2005; 97(7):690-7. DOI: 10.1161/01.RES.0000183881.11739.CB. View

19.

Dong Q, Wright J . Expression of C-reactive protein by alveolar macrophages. J Immunol. 1996; 156(12):4815-20. View

20.

Kaplan M, Hamoud S, Tendler Y, Meilin E, Lazarovitch A, Nitecki S . A significant correlation between C - reactive protein levels in blood monocytes derived macrophages versus content in carotid atherosclerotic lesions. J Inflamm (Lond). 2014; 11(1):7. PMC: 3944991. DOI: 10.1186/1476-9255-11-7. View