Статья
Биохимические маркеры кальцификации атеросклеротических бляшек
В литературном обзоре освещены результаты зарубежных и российских исследований последних лет, посвященных изучению биохимических факторов и потенциальных биомаркеров кальцификации сосудистой стенки, а также атеросклеротических бляшек коронарных и сонных артерий. Результаты проведенных исследований позволяют уточнять и дополнять известные механизмы кальцификации сосудистой стенки. На сегодняшний день наиболее изучены четыре основных биомаркера сосудистой кальцификации – остеопротегерин, остеопонтин, остеонектин и остеокальцин. Таким образом, целью данного обзора явилось систематизирование современных знаний о вкладе вышеперечисленных биохимических маркеров в процессы кальцификации атеросклеротических бляшек, а также выявление потенциальных трендов в использовании данных биомаркеров в современной клинической практике.
1. Gross M.L., Meyer H.P., Ziebart H. et al. Calcification of coronary intima and media: immunohistochemistry, backscatter imaging, and X-ray analysis in renal and nonrenal patients // Clin. J. Am. Soc. Nephrol. 2007. Vol. 2, N 1. P. 121–134.
2. Kurabayashi M. Bone and calcium update; diagnosis and therapy of bone metabolism disease update. Calcification of atherosclerotic plaques: mechanism and clinical significance // Clin. Calcium. 2011. Vol. 21, N 12. P. 43–50. doi: CliCa111217931800
3. Bäck M., Aranyi T., Cancela M.L. et al. Endogenous calcification inhibitors in the prevention of vascular calcification: a consensus statement from the COST action EuroSoftCalcNet // Front. Cardiovasc. Med. 2019. Vol. 18, N 5. P. 196–201. doi: 10.3389/fcvm.2018.00196
4. Di Bartolo B.A., Cartland S.P., Harith H.H. et al. TRAIL-deficiency accelerates vascular calcification in atherosclerosis via modulation of RANKL // PLoS One. 2013. Vol. 8, N 9. P. e74211. doi: 10.1371/journal.pone.0074211
5. Ikeda K., Souma Y., Akakabe Y. et al. Macrophages play a unique role in the plaque calcification by enhancing the osteogenic signals exerted by vascular smooth muscle cells // Biochem. Biophys. Res. Commun. 2012. Vol. 425, N 1. P. 39–44. doi: 10.1016/j.bbrc.2012.07.045
6. Kurabayashi M. Vascular calcification pathological mechanism and clinical application role of vascular smooth muscle cells in vascular calcification // Clin. Calcium. 2015. Vol. 25, N 5. P. 661–669. doi: CliCa1505661669
7. Sugiyama T., Yamamoto E., Fracassi F. et al. Calcified plaques in patients with acute coronary syndromes // JACC Cardiovasc. Interv. 2019. Vol. 12, N 6. P. 531–540. doi: 10.1016/j.jcin.2018.12.013
8. Davaine J.M., Quillard T., Brion R. Osteoprotegerin, pericytes and bone-like vascular calcification are associated with carotid plaque stability // PLoS One. 2014. Vol. 9, N 9. ID e107642. doi: 10.1371/journal.pone.0107642
9. Allison M.A., Hsi S., Wassel C.L. et al. Calcified atherosclerosis in different vascular beds and the risk of mortality // Arterioscler. Thromb. Vasc. Biol. 2012. Vol. 32, N 1. P. 140–146. doi: 10.1161/ATVBAHA.111.235234
10. Pesaro A.E., Katz M., Liberman M. et al. Circulating osteogenic proteins are associated with coronary artery calcification and increase after myocardial infarction // PLoS One. 2018. Vol. 13, N 8. ID e0202738. doi: 10.1371/journal.pone.0202738
11. Quercioli A., Luciano Viviani G., Dallegri F., Mach F., Montecucco F. Receptor activator of nuclear factor kappa B ligand/osteoprotegerin pathway is a promising target to reduce atherosclerotic plaque calcification // Crit. Pathw. Cardiol. 2010. Vol. 9, N 4. P. 227–230. doi: 10.1097/HPC.0b013e318200ec27
12. Ostric M., Kukuljan M., Markić D. et al. Expression of bone-related proteins in vascular calcification and its serum correlations with coronary artery calcification score // J. Biol. Regul. Homeost. Agents. 2019. Vol. 33, N 1. P. 29–38.
13. Вербовой А.Ф., Цанава И.А., Митрошина Е.В., Шаронова Л.А. Остеопротегерин – новый маркер сердечно-сосудистых заболеваний // Терапевт. арх. 2017. Т. 89, № 4. С. 91–94. doi: 10.17116/terarkh201789491-94
14. Rattazzi M., Faggin E., Bertacco E. et al. RANKL expression is increased in circulating mononuclear cells of patients with calcific aortic stenosis // J. Cardiovasc. Transl. Res. 2018. Vol. 11, N 4. P. 329–338. doi: 10.1007/s12265-018-9804-2
15. Mohammadpour A.H., Shamsara J., Nazemi S. et al. Evaluation of RANKL/OPG serum concentration ratio as a new biomarker for coronary artery calcification: A pilot study // Thrombosis. 2012. Vol. 12. ID 306263. doi: 10.1155/2012/306263
16. Quercioli A., Montecucco F., Bertolotto M. et al. Coronary artery calcification and cardiovascular risk: the role of RANKL/OPG signalling // Eur. J. Clin. Invest. 2010. Vol. 40, N 7. P. 645–654. doi: 10.1111/j.13652362.2010.02308.x
17. Rochette L., Meloux A., Rigal E. et al. The role of osteoprotegerin in vascular calcification and bone metabolism: The basis for developing new therapeutics // Calcif. Tissue Int. 2019. Vol. 105, N 3. P. 239–251. doi: 10.1007/s00223-019-00573-6
18. Panizo S., Cardus A., Encinas M. et al. RANKL increases vascular smooth muscle cell calcification through a RANKLBMP4-dependent pathway // Circ. Res. 2009. Vol. 104, N 9. P. 1041–1048. doi: 10.1161/CIRCRESAHA.108.189001
19. Krzanowski M., Krzanowska K., Dumnicka P. et al. Elevated circulating osteoprotegerin levels in the plasma of hemodialyzed patients with severe artery calcification // Ther. Apher. Dial. 2018. Vol. 22, N 5. P. 519–529. doi: 10.1111/1744-9987.12681
20. Ahmed S., Sobh R. Predictive value of osteoprotegerin for early detection coronary artery calcification in type 2 diabetes mellitus patients in correlation with extent of calcification detected by multidetector computed tomography // Endocr. Metab. Immune Disord. Drug Targets. 2019. Vol. 11. P. 256–263. doi: 10.2174/1871530319666190211122858
21. Kwon A., Choi Y.S., Choi Y.W. et al. Serum osteoprotegerin is associated with calcified carotid plaque: a Strobe-Compliant Observational Study // Medicine. 2016. Vol. 95, N 15. ID e3381. doi: 10.1097/MD.0000000000003381
22. Perez de Ciriza C., Moreno M., Restituto P. et al. Circulating osteoprotegerin is increased in the metabolic syndrome and associates with subclinical atherosclerosis and coronary arterial calcification // Clin. Biochem. 2014. Vol. 47, N 18. P. 272–278. doi: 10.1016/j.clinbiochem.2014.09.004
23. Heymann M.F., Herisson F., Davaine J.M. et al. Role of the OPG/RANK/RANKL triad in calcifications of the atheromatous plaques: comparison between carotid and femoral beds // Cytokine. 2012. Vol. 58, N 2. P. 300–306. doi: 10.1016/j.cyto.2012.02.004
24. Icer M.A., Gezmen-Karadag M. The multiple functions and mechanisms of osteopontin // Clin. Biochem. 2018. Vol. 59. P. 17–24. doi: 10.1016/j.clinbiochem.2018.07.003
25. Lok Z.S.Y., Lyle A.N. Osteopontin in vascular disease // Arterioscler. Thromb. Vasc. Biol. 2019. Vol. 39, N 4. P. 613–622. doi: 10.1161/ATVBAHA.118.311577
26. Li X.Y., Chen R., Zhong W. et al. CD137 signaling promotes the formation of plaque calcification via inhibiting the fusion of autophagy and lysosomal in Apo E(-/-) mice // Zhonghua Xin Xue Guan Bing ZaZhi. 2017. Vol. 45, N 12. P. 1078–1085. doi: 10.3760/cma.j.issn.0253-3758.2017.12.013
27. Higgins C.L., Isbilir S., Basto P. et al. Distribution of alkaline phosphatase, osteopontin, RANK ligand and osteoprotegerin in calcifiedhuman carotid atheroma // Protein J. 2015. Vol. 34, N 5. P. 315–328. doi: 10.1007/s10930-015-9620-3
28. Polonskaya Y.V., Kashtanova E.V., Murashov I.S. et al. Associations of osteocalcin, osteoprotegerin, and calcitonin with inflammation biomarkers in atherosclerotic plaques of coronary arteries // Bull. Exp. Biol. Med. 2017. Vol. 162, N 6. P. 726–729. doi: 10.1007/s10517-017-3698-x
29. Ikeda T., Shirasawa T., Esaki Y. et al. Osteopontin mRNA is expressed by smooth muscle-derived foam cells in human atherosclerotic lesions of the aorta // J. Clin. Invest. 1993. Vol. 92, N 6. P. 2814–2820.
30. Dolzhenko A., Richter T., Sagalovsky S. Vascular calcification, atherosclerosis and bone loss (osteoporosis): new pathophysiological mechanisms and future perspectives for pharmacological therapy // Альм. клин. мед. 2016. Т. 44, № 4. С. 513–534.
31. Zwakenberg S.R., van der Schouw Y.T., Schalkwijk C.G., Spijkerman A.M.W., Beulens J.W.J. Bone markers and cardiovascular risk in type 2 diabetes patients // Cardiovasc. Diabetol. 2018. Vol. 17, N 1. P. 45. doi: 10.1186/s12933-018-0691-2
32. Zhang M., Sara J.D., Wang F.L. et al. Increased plasma BMP-2 levels are associated with atherosclerosis burden and coronary calcification in type 2 diabetic patients // Cardiovasc. Diabetol. 2015. Vol. 14. ID 64. doi: 10.1186/s12933-015-0214-3
33. Jeremias Z., Rat N., Benedek I. et al. High iliac calcium score is associated with increased severity and complexity of peripheral arterial disease and predicts global atherosclerotic burden // Vasa. 2018. Vol. 47, N 5. P. 377–386. doi: 10.1024/0301-1526/a000718
34. Rosset E.M., Bradshaw A.D. SPARC/osteonectin in mineralized tissue // Matrix Biol. 2016. Vol. 52-54. P. 78–87. doi: 10.1016/j.matbio.2016.02.001
35. Вербовой А.Ф., Митрошина Е.В., Пашенцева А.В. Взаимосвязь патогенеза атеросклероза и остеопороза // Ожирение и метаболизм. 2016. Т. 13, № 4. С. 8–14. doi: 10.14341/OMET201648-14
36. García-Gómez M.C., Vilahur G. Osteoporosis and vascular calcification: A shared scenario // Clin. Investig. Arterioscler. 2019. Vol. 6. ID S0214. doi: 10.1016/j.arteri.2019.03.008
37. Ciceri P., Elli F., Cappelletti L. Osteonectin (SPARC) expression in vascular calcification: in vitro and ex vivo studies // Calcif. Tissue Int. 2016. Vol. 99, N 5. P. 472–480.
38. Рагино Ю.И., Каштанова Е.В., Чернявский А.М., Волков А.М., Полонская Я.В., Иванова М.В. Связь остеонектина с некоторыми биомаркерами при стенозирующем атеросклерозе и кальцинозе коронарных артерий // Рос. кардиол. журн. 2010. № 4. С. 20–24.
39. Рагино Ю.И., Каштанова Е.В., Чернявский А.М., Полонская Я.В., Воевода М.И. Связь остеонектина с воспалительными, окислительными и липидными биомаркерами при коронарном атеросклерозе и его осложнениях // Атеросклероз и дислипидемии. Рос. кардиол. журн. 2014. № 4. С. 20–25.
40. дрыгина Л.Б., Корсакова Н.Е. Роль белков костного матрикса в регуляции сосудистой кальцификации // Клин.-лаб. консилиум. 2009. № 5. С. 14–20.
41. Evrard S., Delanaye P., Kamel S. et al. Vascular calcification: from pathophysiology to biomarkers // Clin. Chim. Acta. 2015. 438. P. 401–414. doi: 10.1016/j.cca.2014.08.034
42. Akers E.J., Nicholls S.J., Di Bartolo B. A plaque calcification // Arterioscler. Thromb. Vasc. Biol. 2019. Vol. 29. P. 119–125. doi: 10.1161/ATVBAHA.119.311574
43. Emoto M., Mori K., Lee E. et al. Fetuin-A and atherosclerotic calcified plaque in patients with type 2 diabetes mellitus // Metabolism. 2010. Vol. 59, N 6. P. 873–878. doi: 10.1016/j.metabol.2009.10.005
44. Seidu S., Kunutsor S.K., Khunti K. Association of circulating osteocalcin with cardiovascular disease and intermediate cardiovascular phenotypes: systematic review and meta-analysis // Scand. Cardiovasc. J. 2019. Vol. 22. P. 1–10. doi: 10.1080/14017431.2019.1655166
45. Zhang H., Wang L.J., Si D.L. et al. Correlation between osteocalcin-positive endothelial progenitor cells and spotty calcification in patients with coronary artery disease // Clin. Exp. Pharmacol. Physiol. 2015. Vol. 42, N 7. P. 734–739. doi: 10.1111/1440-1681.12366
46. Foresta C., Strapazzon G., De Toni L. et al. Platelets express and release osteocalcin and co-localize in human calcified atherosclerotic plaques // J. Thromb. Haemost. 2013. Vol. 11, N 2. P. 357–365. doi: 10.1111/jth.12088