Analysis of macrophage transcriptome in atherogenesis
https://doi.org/10.15829/1560-4071-2019-2-92-98
Abstract
The accumulation of cholesterol under the influence of modified low density lipoprotein is a key cause of atherogenesis. It is known that atherosclerosis is accompanied by chronic local inflammation. Monocytes/macrophages, main cells of the innate immunity, may not only capturing and accumulating lipids in the vascular wall, but also secreting signaling molecules that affect the functions of other cells. An atherosclerotic lesion is characterized by the inability to complete the inflammatory response, as a result of which the inflammation becomes chronic. Intracellular lipid accumulation is a necessary condition for the initiation of atherogenesis, but it is not known whether it is sufficient. Analysis of the transcriptome allowed us to characterize the state of macrophages loaded with lipids. Studies presented in this review show that the reaction of innate immunity contributes to the accumulation of intracellular lipids and aggravates it.
Keywords
atherosclerosis,
macrophages,
transcriptome analysis,
activation,
low density lipoproteins,
gene expression
Supporting agencies: Russian Foundation for Basic Research, № 18-34-00997
About the Authors
M. V. Kubekina
Institute of Gene Biology; The Institute of General Pathology and Pathophysiology
Russian Federation
Competing Interests:
Russian Federation
Moscow
Competing Interests:
nothing to declare
N. G. Nikiforov
Institute of Gene Biology; National Medical Research Center of Cardiology; The Institute of General Pathology and Pathophysiology
Russian Federation
Competing Interests:
Russian Federation
Moscow
Competing Interests:
nothing to declare
V. P. Karagodin
Plekhanov Russian University of Economics
Russian Federation
Competing Interests:
Russian Federation
Moscow
Competing Interests:
nothing to declare
I. A. Sobenin
National Medical Research Center of Cardiology
Russian Federation
Competing Interests:
Russian Federation
Moscow
Competing Interests:
nothing to declare
A. N. Orekhov
The Institute of General Pathology and Pathophysiology; Scientific Institute of Atherosclerosis Research
Russian Federation
Competing Interests:
Russian Federation
Moscow; Skolkovo
Competing Interests:
nothing to declare
References
1. Gratchev AV, Sobenin IA, Orekhov AN, et al. Monocytes as a diagnostic marker of cardiovascular diseases. Immunobiology. 2012;217(5):476-82. doi: 10.1016/j.imbio.2012.01.008.
2. Chistiakov DA, Bobryshev YV, Orekhov AN. Macrophage-mediated cholesterol handling in atherosclerosis. J Cell Mol. Med. 2016;20(1):17-28. doi:10.1111/jcmm.12689.
3. Orekhov AN, Nikiforov NG, Elizova NV, et al. Phenomenon of individual difference in human monocyte activation. Exp. Mol. Pathol. 2015;99(1): 151-4. doi: 10.1016/j.yexmp.2015.06.011.
4. Gratchev A, Ovsiy I, Manousaridis I, et al. Novel Monocyte Biomarkers of Atherogenic Conditions. Curr. Pharm. Des. 2013;19(33)5859-64.
5. Varin A, Gordon S. Alternative activation of macrophages: immune function and cellular biology. Immunobiology. 2009;214:630-41. doi:10.1016/j.imbio.2008.11.009.
6. Brocheriou I, Maouche S, Durand H, et al. Antagonistic regulation of macrophage phenotype by M-CSF and GM-CSF: implication in atherosclerosis. Atherosclerosis. 2011;214:316-24. doi:10.1016/j.atherosclerosis.2010.11.023.
7. Stoger JL, Gijbels MJ, van der Velden S, et al. Distribution of macrophage polarization markers in human atherosclerosis. Atherosclerosis. 2012;225(2):461-8. doi: 10.1016/j.atherosclerosis.2012.09.013.
8. Cho KY, Miyoshi H, Kuroda S, et al. The phenotype of infiltrating macrophages influences arteriosclerotic plaque vulnerability in the carotid artery. J Stroke Cerebrovasc Dis. 2013;22(7):910-8. doi:10.1016/j.jstrokecerebrovasdis.2012.11.020.
9. Aladinsky VA, Nikiforov NG, Orekhova VA, et al. Direct antiatherosclerotic therapy: possible approaches, results of clinical trials. Patol Fiziol Eksp Ter. 2013;(4):76-83. (In Russ)
10. Chinetti-Gbaguidi G, Colin S, Staels B. Macrophage subsets in atherosclerosis. Nat Rev Cardiol. 2015;12:10-7. doi:10.1038/nrcardio.2014.173.
11. Biswas SK, Chittezhath M, Shalova IN, et al. Macrophage polarization and plasticity in health and disease. Immunol Res. 2012;11-24. doi:10.1007/s12026-012-8291-9.
12. Bouhlel MA, Derudas B, Rigamonti E, et al. PPARgamma activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties. Cell Metab. 2007;6:137-43.
13. Chinetti-Gbaguidi G, Baron M, Bouhlel MA, et al. Human atherosclerotic plaque alternative macrophages display low cholesterol handling but high phagocytosis because of distinct activities of the PPARgamma and LXRalpha pathways. Circ Res. 2011;108:985-95. doi:10.1161/CIRCRESAHA.110.233775.
14. Tall AR, Yvan-Charvet L. Cholesterol, inflammation and innate immunity. Nat Rev Immunol. 2015;15:104-16. doi:10.1038/nri3793.
15. Biswas SK, Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol. 2010;11:889-96. doi:10.1038/ni.1937.
16. da Silva RF, Lappalainen J, Lee-Rueckert M, Kovanen PT. Conversion of human M-CSF macrophages into foam cells reduces their proinflammatory responses to classical M1-polarizing activation. Atherosclerosis. 2016;248;170-8. doi:10.1016/j.atherosclerosis.2016.03.012.
17. Byron SA, van Keuren-Jensen KR, Engelthaler DM, et al. Translating RNA sequencing into clinical diagnostics: Opportunities and challenges. Nat. Rev. Genet. 2016;17:257-71. doi:10.1038/nrg.2016.10.
18. Barrans JD, Allen PD, Stamatiou D, et al. Global gene expression profiling of end-stage dilated cardiomyopathy using a human cardiovascular-based cDNA microarray. Am. J. Pathol. 2002;160:2035-43.
19. Malone JH, Oliver B. Microarrays, deep sequencing and the true measure of the transcriptome. BMC Biol. 2011;9:34. doi:10.1186/1741-7007-9-34.
20. Rienzo M, Casamassimi A, Schiano C, et al. Distinct alternative splicing patterns of mediator subunit genes during endothelial progenitor cell differentiation. Biochimie. 2012;94:1828-32. doi:10.1016/j.biochi.2012.04.008.
21. Murphy J, Bustin SA. Reliability of real-time reverse-transcription PCR in clinical diagnostics: Gold standard or substandard? Expert Rev. Mol. Diagn. 2009;9:187-97. doi:10.1586/14737159.9.2.187.
22. Cao L, Cui X, Hu J, et al. Advances in digital polymerase chain reaction (dPCR) and its emerging biomedical applications. Biosens. Bioelectron. 2017;90:459-74. doi:10.1016/j.bios.2016.09.082.
23. Rai G, Rai R, Saeidian AH, et al. Microarray to deep sequencing: transcriptome and miRNA profiling to elucidate molecular pathways in systemic lupus erythematosus. Immunol Res. 2016;64(1):14-24. doi:10.1007/s12026-015-8672-y.
24. Farkas MH, Grant GR, White JA, et al. Transcriptome analyses of the human retina identify unprecedented transcript diversity and 3.5 Mb of novel transcribed sequence via significant alternative splicing and novel genes. BMC Genomics. 2013;14:486. doi:10.1186/1471-2164-14-486.
25. Lyu Y, Yang Y, Liu Y, et al. Analysis of a patient with X-linked mental retardation by next generation sequencing. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2018;35(2):257-60. doi:10.3760/cma.j.issn.1003-9406.2018.02.025.
26. Kesherwani V, Shahshahan HR, Mishra PK. Cardiac transcriptome profiling of diabetic Akita mice using microarray and next generationsequencing. PLoS One. 2017; 12(8). doi:10.1371/journal.pone.0182828.eCollection 2017.
27. Martinez FO, Gordon S, Locati M, et al. Transcriptional profiling of the human monocyto-macrophage differentiation and polarization: new molecules and patterns of gene expression. J Immunol. 2006;177:7303-11.
28. Adamson S, Leitinger N. Phenotypic modulation of macrophages in response to plaque lipids. Curr Opin Lipidol. 2011;22:335-42. doi:101097/MOL.0b013e32834a97e4.
29. Zhang YP, Pan CS, Yan L, et al. Catalpol restores LPS-elicited rat microcirculation disorder by regulation of a network of signaling involving inhibition of TLR-4 and SRC. Am J Physiol Gastrointest Liver Physiol. 2016;311(6):G1091-G1104. doi:10.1152/ajpgi.00159.2016.
Review
For citations:
Kubekina M.V., Nikiforov N.G., Karagodin V.P., Sobenin I.A., Orekhov A.N. Analysis of macrophage transcriptome in atherogenesis. Russian Journal of Cardiology. 2019;(2):92-98. (In Russ.) https://doi.org/10.15829/1560-4071-2019-2-92-98
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