MicroRNA as significant biomarkers of cerebrovascular atherosclerosis

封面

如何引用文章

全文:

详细

Introduction. Carotid atherosclerosis (CA) is one of the main causes of ischaemic stroke. MicroRNA is a relatively new group of biomarkers, some of which are associated with atherogenesis.

The aim of the study was to evaluate the expression of several microRNAs in patients with cerebrovascular disease, depending on the severity of CA.

Materials and methods. The study included 50 people (median age 66 [61; 71] years, 58% men) with cerebrovascular disease secondary to CA. The patients were divided into two groups: 16 patients (32%) had ≥70% internal carotid artery (ICA) stenosis (main group), while the remaining 34 patients had <70% stenosis and formed the comparison group. Expression of the following microRNAs was measured: miR-126-5p, miR-126-3p, miR-29-5p, miR-29-3p, miR-33a-5p, miR-33a-3p, miR-21-5p and miR-21-3p.

Results. Compared to the comparison group, patients with a high degree of CA had reduced expression of miR-126-5p/-3p (4.8 and 5.9 vs. 8.5 and 7.6, respectively; p < 0.001) and miR-29-3p (7.6 vs. 10.3; p < 0.001), while miR-33a-5p expression was elevated (46.3 vs. 40.0; p < 0.05). Cluster analysis confirmed typical expression patterns of these microRNAs in patients with varying degrees of ICA stenosis. Significant negative correlations were also found between the degree of stenosis and expression of miR-126-5p (ρ = –0.83; р < 0.05), miR-126-3p (ρ = –0.64; р < 0.05) and miR-29-3p (ρ = –0.62; р < 0.05).

Conclusion. Based on an analysis of patients with cerebral atherosclerosis, the studied microRNAs can be divided into proatherogenic (miR-33a-5p/-3p) and atheroprotective (miR-126-5p/-3p, miR-29-3p, and mir-21-5p/-3p). These biomarkers can be diagnostically useful in predicting the risk of both CA progression and acute cerebrovascular accidents, yet prospective studies are required.

作者简介

Anton Raskurazhev

Research Center of Neurology

编辑信件的主要联系方式.
Email: rasckey@live.com
ORCID iD: 0000-0003-0522-767X

Cand. Sci. (Med.), neurologist, researcher, 1st Neurology department

俄罗斯联邦, Moscow

Alla Shabalina

Research Center of Neurology

Email: ashabalina@yandex.ru
ORCID iD: 0000-0001-9604-7775

D. Sci. (Med.), leading researcher, Head, Laboratory of hemorheology, hemostasis and pharmacokinetics (with clinical laboratory diagnostics)

俄罗斯联邦, Moscow

Polina Kuznetsova

Research Center of Neurology

Email: angioneurology0@gmail.com
ORCID iD: 0000-0002-4626-6520

Cand. Sci. (Med.), neurologist, researcher, 1st Neurology department

俄罗斯联邦, Moscow

Marine Tanashyan

Research Center of Neurology

Email: M_Tanashyan2004@mail.ru
ORCID iD: 0000-0002-5883-8119

D. Sci. (Med.), Prof., Corresponding member of RAS, Deputy Director for science, Head, 1st Neurological department

俄罗斯联邦, Moscow

参考

  1. Song P., Fang Z., Wang H. et al. Global and regional prevalence, burden, and risk factors for carotid atherosclerosis: a systematic review, meta-analysis, and modelling study. Lancet Glob Health. 2020;8(5):e721–e729. doi: 10.1016/S2214-109X(20)30117-0. PMID: 32353319.
  2. Wu M.Y., Li C.J., Hou M.F., Chu P.Y. New insights into the role of inflammation in the pathogenesis of atherosclerosis. Int J Mol Sci. 2017;18(10):2034. doi: 10.3390/ijms18102034. PMID: 28937652.
  3. Tanashyan M.M., Raskurazhev A.A., Shabalina A.A. et al. [Biomarkers of cerebral atherosclerosis: the capabilities of early diagnosis and prognosis of individual risk]. Annals of clinical and experimental neurology. 2015;9(3):20–25. (In Russ.)
  4. Tanashyan M.M., Raskurazhev A.A., Shabalina A.A., Lagoda O.V. Sposob diagnostiki techenija “asimptomnogo” karotidnogo ateroskleroza. Patent RF, no. 2592237, 2016. (In Russ.)
  5. Raskurazhev A.A., Tanashyan M.M. [The role of micro-RNA in cerebrovascular disease]. Annals of clinical and experimental neurology. 2019;13(3):41–46. doi: 10.25692/ACEN.2019.3.6. (In Russ.)
  6. Tajbakhsh A., Bianconi V., Pirro M. et al. Efferocytosis and atherosclerosis: regulation of phagocyte function by MicroRNAs. Trends Endocrinol. Metab. 2019;30(9):672–683. doi: 10.1016/j.tem.2019.07.006. PMID: 31383556.
  7. Raskurazhev A.A., Tanashyan M.M., Shabalina A.A. et al. Micro-RNA in patients with carotid atherosclerosis. Hum Physiol. 2020;46:880–885. doi: 10.1134/S0362119720080113.
  8. Howard D.P.J., Gaziano L., Rothwell P.M., Oxford Vascular Study. Risk of stroke in relation to degree of asymptomatic carotid stenosis: a population-based cohort study, systematic review, and meta-analysis. Lancet Neurol. 2021;20(3):193-202. doi: 10.1016/S1474-4422(20)30484-1. PMID: 33609477.
  9. Kim S.H., Kim G.J., Umemura T. et al. Aberrant expression of plasma microRNA-33a in an atherosclerosis-risk group. Mol Biol Rep. 2017;44(1):79–88. doi: 10.1007/s11033-016-4082-z. PMID: 27664032.
  10. Marquart T.J., Allen R.M., Ory D.S., Baldán A. miR-33 links SREBP-2 induction to repression of sterol transporters. Proc Natl Acad Sci U S A. 2010;107(27):12228–32. doi: 10.1073/pnas.1005191107. PMID: 20566875.
  11. Horie T., Baba O., Kuwabara Y. et al. MicroRNA-33 deficiency reduces the progression of atherosclerotic plaque in ApoE-/- mice. J Am Heart Assoc. 2012;1(6):e003376. doi: 10.1161/JAHA.112.003376. PMID: 23316322.
  12. Kim J., Yoon H., Horie T. et al. microRNA-33 Regulates ApoE lipidation and amyloid-β metabolism in the brain. J Neurosci. 2015;35(44):14717-26. doi: 10.1523/JNEUROSCI.2053-15.2015. PMID: 26538644.
  13. Bretschneider M., Busch B., Mueller D. et al. Activated mineralocorticoid receptor regulates micro-RNA-29b in vascular smooth muscle cells. FASEB J. 2016;30(4):1610–1622. doi: 10.1096/fj.15-271254. PMID: 26728178.
  14. Silambarasan M., Tan J.R., Karolina D.S. et al. MicroRNAs in hyperglycemia induced endothelial cell dysfunction. Int J Mol Sci. 2016;17(4):518. doi: 10.3390/ijms17040518. PMID: 27070575.
  15. Huang Y., Li J., Chen J. et al. The association of circulating MiR-29b and interleukin-6 with subclinical atherosclerosis. Cell Physiol Biochem. 2017;44:1537–1544. doi: 10.1159/000485649. PMID: 29197872.
  16. Ulrich V., Rotllan N., Araldi E. et al. Chronic miR-29 antagonism promotes favorable plaque remodeling in atherosclerotic mice. EMBO Mol Med. 2016;8(6):643–653. doi: 10.15252/emmm.201506031. PMID: 27137489.
  17. Deng X., Chu X., Wang P. et al. MicroRNA-29a-3p reduces TNFα-induced endothelial dysfunction by targeting tumor necrosis factor receptor 1. Mol Ther Nucleic Acids. 2019;18:903–915. doi: 10.1016/j.omtn.2019.10.014. PMID: 31760375.
  18. Yu B., Jiang Y., Wang X., Wang S. An integrated hypothesis for miR-126 in vascular disease. Med Res Arch. 2020;8(5):2133. doi: 10.18103/mra.v8i5.2133. PMID: 34222652.
  19. Harris T.A., Yamakuchi M., Ferlito M. et al. MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1. Proc Natl Acad Sci U S A. 2008;105(5):1516–1521. doi: 10.1073/pnas.0707493105. PMID: 18227515.
  20. Canfrán-Duque A., Rotllan N., Zhang X. et al. Macrophage deficiency of miR-21 promotes apoptosis, plaque necrosis, and vascular inflammation during atherogenesis. EMBO Mol Med. 2017;9(9):1244–1262. doi: 10.15252/emmm.201607492. PMID: 28674080.
  21. Jin H., Li D.Y., Chernogubova E. et al. Local Delivery of miR-21 Stabilizes Fibrous caps in vulnerable atherosclerotic lesions. Mol Ther. 2018;26(4):1040–1055. doi: 10.1016/j.ymthe.2018.01.011. PMID: 29503197.
  22. Cengiz M., Yavuzer S., Kılıçkıran Avcı B. et al. Circulating miR-21 and eNOS in subclinical atherosclerosis in patients with hypertension. Clin Exp Hypertens. 2015;37(8):643–649. doi: 10.3109/10641963.2015.1036064. PMID: 26114349.

补充文件

附件文件
动作
1. JATS XML
下载

版权所有 © Raskurazhev A.A., Shabalina A.A., Kuznetsova P.I., Tanashyan M.M., 2022

Creative Commons License
此作品已接受知识共享署名 4.0国际许可协议的许可
##common.cookie##