Proteomic studies in coronary atherosclerosis
https://doi.org/10.20538/1682-0363-2026-1-163-175
Abstract
Proteomic studies have made a significant contribution to the study of the pathogenesis of cardiovascular diseases, creating the basis for the development of new potential biomarkers for assessing the risk of developing diseases and their complications. We analyzed the main foreign and domestic publications over the past 15 years using the PubMed/Medline and RSCI/elibrary.ru databases and summarized the available data on proteomic studies in the field of atherosclerotic cardiovascular diseases and coronary atherosclerosis. In this literature review, priority was given to studies on the search for new proteomic biomarkers of coronary atherosclerosis, including proteomic markers of unstable atherosclerotic plaques. The data from our own proteomic studies on potential biomarkers of coronary atherosclerosis are presented.
About the Authors
E. M. Stakhneva
Research Institute of Internal and Preventive Medicine – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
Russian Federation
Russian Federation
175/1 Bogatkov St., 630089 Novosibirsk, Russian Federation
Yu. I. Ragino
Research Institute of Internal and Preventive Medicine – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
Russian Federation
Russian Federation
175/1 Bogatkov St., 630089 Novosibirsk, Russian Federation
E. V. Kashtanova
Research Institute of Internal and Preventive Medicine – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
Russian Federation
Russian Federation
175/1 Bogatkov St., 630089 Novosibirsk, Russian Federation
Ya. V. Polonskaya
Research Institute of Internal and Preventive Medicine – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
Russian Federation
Russian Federation
175/1 Bogatkov St., 630089 Novosibirsk, Russian Federation
References
1. Wolf D., Ley K. Immunity and inflammation in atherosclerosis. Circ. Res. 2019;124(2):315–327. DOI: 10.1161/CIRCRESAHA.118.313591.
2. Tsao C.W., Aday A.W., Almarzooq Z.I. Alonso A., Beaton A.Z., Bittencourt M.S. et al. Heart Disease and Stroke Statistics-2022 Update: A Report From the American Heart Association. Circulation. 2022;145(8):e153–e639. DOI: 10.1161/CIR.0000000000001052.
3. Bobryshev Y.V. Monocyte recruitment and foam cell formation in atherosclerosis. Micron. 2006;37:208–222. DOI: 10.1016/j.micron.2005.10.00.
4. Bentzon J.F., Otsuka F., Virmani R., Falk E. Mechanisms of plaque formation and rupture. Circ. Res. 2014;114(12):1852–1866. DOI: 10.1161/CIRCRESAHA.114.302721.
5. Mohamed Bakrim N., Mohd Shah A.N.S., Talib N.A., Ab Rahman J., Abdullah A. Identification of haptoglobin as a potential biomarker in young adults with acute myocardial infarction by proteomic analysis. Malays. J. Med. Sci. 2020;27(2):64–76. DOI: 10.21315/mjms2020.27.2.8.
6. Navas-Carrillo D., Marín F., Valdés M., Orenes-Piñero E. Deciphering acute coronary syndrome biomarkers: High-resolution proteomics in platelets, thrombi and microparticles. Crit. Rev. Clin. Lab. Sci. 2017;54(1):49–58. DOI: 10.1080/10408363.2016.1241214.
7. Stöhr R., Schurgers L., van Gorp R., Jaminon A., Marx N. Reutelingsperger C. Annexin A5 reduces early plaque formation in ApoE –/– mice. PLoS One. 2017;12(12):e0190229. DOI: 10.1371/journal.pone.0190229.
8. Bagnato C., Thumar J., Mayya V., Hwang S.I., Zebroski H., Claffey K.P. et al. Proteomics analysis of human coronary atherosclerotic plaque: a feasibility study of direct tissue proteomics by liquid chromatography and tandem mass spectrometry. Mol. Cell Proteomics. 2007;6(6):1088–1102. DOI: 10.1074/mcp.M600259-MCP200.
9. Zhou Y., Yuan J., Fan Y., An F., Chen J., Zhang Y. et al. Proteomic landscape of human coronary artery atherosclerosis. Int. J. Mol. Med. 2020;46(1):371–383. DOI: 10.3892/ijmm.2020.4600.
10. Malaud E., Merle D., Piquer D., Molina L., Salvetat N., Rubrecht L. et al. Local carotid atherosclerotic plaque proteins for the identification of circulating biomarkers in coronary patients. Atherosclerosis. 2014;233(2):551–558. DOI: 10.1016/j.atherosclerosis.2013.12.019.
11. Lee R., Fischer R., Charles P.D., Adlam D., Valli A., Di Gleria K. et al. A novel workflow combining plaque imaging, plaque and plasma proteomics identifies biomarkers of human coronary atherosclerotic plaque disruption. Clin. Proteomics. 2017;14:22. DOI: 10.1186/ s12014-017-9157-x.
12. Stakhneva E.M., Meshcheryakova I.A., Demidov E.A., Starostin K.V., Sadovski E.V., Peltek S.E. et al. A proteomic study of atherosclerotic plaques in men with coronary atherosclerosis. Diagnostics. 2019;9(4):177. DOI: 10.3390/diagnostics9040177.
13. Herrington D.M., Mao C., Parker S.J., Fu Z., Yu G., Chen L. et al. Proteomic architecture of human coronary and aortic atherosclerosis. Circulation. 2018;137(25):2741–2756. DOI: 10.1161/CIRCULATIONAHA.118.034365.
14. Han Y., Zhao S., Gong Y., Hou G., Li X., Li L. Serum cyclin-dependent kinase 9 is a potential biomark- er of atherosclerotic inflammation. Oncotarget. 2016;7(2):1854–1862. DOI: 10.18632/ oncotarget.6443.
15. Lepedda A.J., Cigliano A., Cherchi G.M., Spirito R., Maggioni M., Carta F. et al. A proteomic approach to differentiate histologically classified stable and unstable plaques from human carotid arteries. Atherosclerosis. 2009;203(1):112–118. DOI: 10.1016/j.atherosclerosis.2008.07.001.
16. Olson F.J., Sihlbom C., Davidsson P., Hulthe J., Fagerberg B., Bergström G. Consistent differences in protein distribution along the longitudinal axis in symptomatic carotid atherosclerotic plaques. Biochem. Biophys. Res. Commun. 2010;401(4):574–580. DOI: 10.1016/j.bbrc.2010.09.103.
17. Rocchiccioli S., Pelosi G., Rosini S., Marconi M., Viglione F., Citti L. et al. Secreted proteins from carotid endarterectomy: an untargeted approach to disclose molecular clues of plaque progression. J. Transl. Med. 2013;11:260. DOI: 10.1186/1479-5876-11-260.
18. Seki T., Saita E., Kishimoto Y., Ibe S., Miyazaki Y., Miura K. et al. Low levels of plasma osteoglycin in patients with complex coronary lesions. J. Atheroscler. Thromb. 2018;25(11):1149–1155. DOI: 10.5551/jat.43059.
19. Cheng J.M., Akkerhuis K.M., Meilhac O., Oemrawsingh R.M., Garcia-Garcia H.M., van Geuns R.J. et al. Circulating osteoglycin and NGAL/MMP9 complex concentrations predict 1-year major adverse cardiovascular events after coronary angiography. Arterioscler. Thromb. Vasc. Biol. 2014;34(5):1078–1084. DOI: 10.1161/ATVBAHA.114.303486.
20. Chistiakov D.A., Orekhov A.N., Bobryshev Y.V. Endothelial barrier and its abnormalities in cardiovascular disease. Front. Physiol. 2015;6:365. DOI: 10.3389/fphys.2015.00365.
21. Tu Z.L., Yu B., Huang D.Y., Ojha R., Zhou S.K., An H.D. et al. Proteomic analysis and comparison of intra- and extracranial cerebral atherosclerosis responses to hyperlipidemia in rabbits. Mol. Med. Rep. 2017;16(3):2347–2354. DOI: 10.3892/mmr.2017.6869.
22. Matyushenko A.M., Koubassova N.A., Shchepkin D.V., Kopylova G.V., Nabiev S.R., Nikitina L.V. et al. The effects of cardiomyopathy-associated mutations in the head-to-tail overlap junction of α-tropomyosin on its properties and interaction with actin. Int. J. Biol. Macromol. 2019;125:1266–1274. DOI: 10.1016/j.ijbiomac.2018.09.105.
23. Dirajlal-Fargo S., Kulkarni M., Bowman E., Shan L., Sattar A., Funderburg N. et al. Serum albumin is associated with higher inflammation and carotid atherosclerosis in treated human immunodeficiency virus infection. Open Forum Infect. Dis. 2018;5(11):ofy291. DOI: 10.1093/ofid/ofy291.
24. Lin P., Ji H.H., Li Y.J., Guo S.D. Macrophage plasticity and atherosclerosis therapy. Front. Mol. Biosci. 2021;8:679797. DOI: 10.3389/fmolb.2021.679797.
25. Gordon S., Martinez F.O. Alternative activation of macrophages: Mechanism and functions. Immunity. 2010;32(5):593–604. DOI: 10.1016/j.immuni.2010.05.007.
26. Murray P.J., Wynn T.A. Protective and pathogenic functions of macrophage subsets. Nat. Rev. Immunol. 2011;11(11):723–737. DOI: 10.1038/nri3073.
27. Wang L.X., Zhang S.X., Wu H.J., Rong X.L., Guo J. M2b macrophage polarization and its roles in diseases. J. Leukoc. Biol. 2019;106(2):345–358. DOI: 10.1002/JLB.3RU1018-378RR.
28. Zizzo G., Hilliard B.A., Monestier M., Cohen P.L. Efficient clearance of early apoptotic cells by human macrophages requires M2c polarization and MerTK induction. J. Immunol. 2012;189(7):3508–3520. DOI: 10.4049/jimmunol.1200662.
29. Ferrante C.J., Pinhal-Enfield G., Elson G., Cronstein B.N., Hasko G., Outram S., Leibovich S.J. The adenosine-dependent angiogenic switch of macrophages to an M2-like phenotype is independent of interleukin-4 receptor alpha (IL-4Ralpha) signaling. Inflammation. 2013;36(4):921–931. DOI: 10.1007/s10753-013-9621-3.
30. Nielsen M.J., Moller H.J., Moestrup S.K. Hemoglobin and heme scavenger receptors. Antioxid. Redox. Signal. 2010;12(2):261–273. DOI: 10.1089/ars.2009.2792.
31. Boyle J.J. Heme and haemoglobin direct macrophage Mhem phenotype and counter foam cell formation in areas of intraplaque haemorrhage. Curr. Opin. Lipidol. 2012;23(5):453–461. DOI: 10.1097/MOL.0b013e328356b145.
32. Boyle J.J., Johns M., Kampfer T., Nguyen A.T., Game L., Schaer D.J. et al. Activating transcription factor 1 directs Mhem atheroprotective macrophages through coordinated iron handling and foam cell protection. Circ. Res. 2012;110(1):20–33. DOI: 10.1161/CIRCRESAHA.111.247577.
33. Stoger J.L., Gijbels M.J., van der Velden S., Nguyen A.T., Game L., Schaer D.J. et al. Distribution of macrophage polarization markers in human atherosclerosis. Atherosclerosis. 2012;225(2):461–468. DOI: 10.1016/j.atherosclerosis.2012.09.013.
34. Cho K.Y., Miyoshi H., Kuroda S., Yasuda H., Kamiyama K., Nakagawara J. et al. The phenotype of infiltrating macrophages influences arteriosclerotic plaque vulnerability in the carotid artery. J. Stroke Cereb. Dis. 2013;22(7):910–918. DOI: 10.1016/j.jstrokecerebrovasdis.2012.11.020.
35. Chinetti-Gbaguidi G., Colin S., Staels B. Macrophage subsets in atherosclerosis. Nat. Rev. Cardiol. 2015;12(1):10–17. DOI: 10.1038/nrcardio.2014.173.
36. Barrett T.J. Macrophages in atherosclerosis regression. Arter. Thromb. Vasc. Biol. 2020;40(1):20–33. DOI: 10.1161/ATVBAHA.119.312802.
37. De Gaetano M., Crean D., Barry M., Belton O. M1- and M2-type macrophage responses are predictive of adverse outcomes in human atherosclerosis. Front. Immunol. 2016;7:275. DOI: 10.3389/fimmu.2016.00275.
38. Vaisar T., Hu J.H., Airhart N., Fox K., Heinecke J., Nicosia R.F. et al. Parallel murine and human plaque proteomics reveals pathways of plaque rupture. Circ. Res. 2020;127(8):997–1022. DOI: 10.1161/CIRCRESAHA.120.317295.
39. Baetta R., Banfi C. Dkk (dickkopf) proteins. Arter. Thromb. Vasc. Biol. 2019;39(7):1330–1342. DOI: 10.1161/ATVBAHA.119.312612.
40. Stakhneva E.M., Meshcheryakova I.A., Demidov E.A., Starostin K.V., Peltek S.E., Voevoda M.I., Ragino Y.I. Changes in the proteomic profile of blood serum in coronary atherosclerosis. J. Med. Biochem. 2020;39(2):208–214. DOI: 10.2478/jomb-2019-0022.
41. Patzelt J., Verschoor A., Langer H.F. Platelets and the complement cascade in atherosclerosis. Front. Physiol. 2015;6:49. DOI: 10.3389/fphys.2015.00049.
42. Teoh C.L., Griffin M.D., Howlett G.J. Apolipoproteins and amyloid fibril formation in atherosclerosis. Protein Cell. 2011;2(2):116–127. DOI: /10.1007/s13238-011-1013-6.
43. Cubedo J., Padró T., Alonso R., Cinca J., Mata P., Badimon L. Differential proteomic distribution of TTR (pre-albumin) forms in serum and HDL of patients with high cardiovascular risk. Atherosclerosis. 2012;222(1):263–269. DOI: 10.1016/j.atherosclerosis.2012.02.024.
44. Li F., Xia K., Li C., Yang T. Retinol-binding protein 4 as a novel risk factor for cardiovascular disease in patients with coronary artery disease and hyperinsulinemia. Am. J. Med. Sci. 2014;348(6):474–479. DOI: 10.1097/MAJ.0000000000000347.
45. Lambadiari V., Kadoglou N.P., Stasinos V., Maratou E., Antoniadis A., Kolokathis F. et al. Serum levels of retinol-binding protein-4 are associated with the presence and severity of coronary artery disease. Cardiovasc. Diabetol. 2014;13:121. DOI: 10.1186/s12933-014-0121-z.
46. Vinchi F., Muckenthaler M.U., Da Silva M.C., Balla G., Balla J., Jeney V. Atherogenesis and iron: from epidemiology to cellular level. Front. Pharmacol. 2014;5:94. DOI: 10.3389/fphar.2014.00094.
47. Mehta N.U., Reddy S.T. Role of hemoglobin/heme scavenger protein hemopexin in atherosclerosis and inflammatory diseases. Curr. Opin. Lipidol. 2015;26(5):384–387. DOI: 10.1097/MOL.0000000000000208.
48. Daybanyrova L.V., Shevchenko O.P. Clinical significance levels of C-reactive protein and ceruloplasmin in patients with ischemic heart disease. Wiad Lek. 2015;68(4):517–519.
49. Dadu R.T., Dodge R., Nambi V., Virani S.S., Hoogeveen R.C., Smith N.L. et al. Ceruloplasmin and heart failure in the Atherosclerosis Risk in Communities study. Circ. Heart Fail. 2013;6(5):936–943. DOI: 10.1161/CIRCHEARTFAILURE.113.000270.
50. Stakhneva E.M., Meshcheryakova I.A., Demidov E.A., Starostin K.V., Ragino Y.I., Peltek S.E. et al. Proteomic study of blood serum in coronary atherosclerosis. Bull. Exp. Biol. Med. 2017;162(3):343–345. DOI: 10.1007/s10517-017-3611-7.
51. Kim K.H., Ahn Y.H., Ji E.S., Lee J.Y., Kim J.Y., An H.J. et al. Quantitative analysis of low-abundance serological proteins with peptide affinity-based enrichment and pseudo-multiple reaction monitoring by hybrid quadrupole time-of-flight mass spectrometry. Analytica Chimica Acta. 2015;882:38–48. DOI: 10.1016/j.aca.2015.04.033.
52. Стахнёва Е.М., Каштанова Е.В., Полонская Я.В., Гарбузова (Стрюкова) Е.В., Шрамко В.С., Садовский Е.В. и др. Связь белков острой фазы в крови с наличием нестабильных атеросклеротических бляшек при коронарном атеросклерозе. Профилактическая медицина. 2023;26(8):76–81. DOI: 10.17116/profmed20232608176.
53. Стахнёва Е.М., Мещерякова И.А., Демидов Е.А., Старостин К.В., Садовский Е.В., Пельтек С.Е. и др. Сравнение белкового состава атеросклеротических бляшек коронарных артерий на разных стадиях развития. Молекулярная медицина. 2021;19(5):58–64. DOI: 10.29296/24999490-2021-05-09.
Review
For citations:
Stakhneva E.M., Ragino Yu.I., Kashtanova E.V., Polonskaya Ya.V. Proteomic studies in coronary atherosclerosis. Bulletin of Siberian Medicine. 2026;25(1):163-175. https://doi.org/10.20538/1682-0363-2026-1-163-175
Views:
129
JATS XML
Email this article 