Metabolic markers of cerebrovascular pathology


DOI: https://dx.doi.org/10.18565/therapy.2024.5.84-92

Tanashyan M.M., Antonova K.V., Spryshkov N.E., Panina A.A.

Scientific Center of Neurology, Moscow
Abstract. Aspects of correlation between cerebrovascular diseases (CVD) and metabolic disorders that are extremely actual due to the pandemic increase of the incidence of obesity (OB) and diabetes mellitus (DM) are discussed in the article. The number of brain strokes in the world and problems of associated medical and social consequences are constantly increasing. The problem of effective primary prevention of CVD has not been solved, which determines the need for stratification of high-risk individuals and early diagnosis of vascular cerebral pathology. Influence of a wide range of biologically active molecules associated with obesity and diabetes mellitus at the development of cerebral vascular pathology has been shown; pro-inflammatory, pro-atherogenic and pro-thrombogenic effects of metabolic disorders have been fixed. Determining a biomarker panel of cerebrometabolic pathology may become a significant milestone in the development of strategies for the prevention and treatment of cerebrovascular diseases.

Literature


1. Пирадов М.А., Танашян М.М., Максимова М.Ю. Инсульт: современные технологии диагностики и лечения. М.: МЕДпресс-информ. 2018; 360 с. (Piradov M.A., Tanashyan M.M., Maksimova M.Yu. Stroke: Modern technologies of diagnosis and treatment. Moscow: MEDpress-inform. 2018; 360 pp. (In Russ.)). ISBN 978-5-00-030622-2. EDN: YSAJRZ.


2. Feigin V., Brainin M., Norrving B. et al. World Stroke Organization (WSO): Global Stroke Fact Sheet 2022. Int J Stroke. 2022; 17(1): 18–29.


https://doi.org/10.1177/17474930211065917. PMID: 34986727.


3. Ануфриев П.Л., Танашян М.М., Гулевская Т.С., Евдокименко А.Н. Морфологические маркеры основных патогенетических вариантов ишемических инсультов при церебральном атеросклерозе. Анналы клинической и экспериментальной неврологии. 2018; 12(4): 16–22. (Anufriev P.L., Tanashyan M.M., Gulevskaya T.S., Evdokimenko A.N. Morphological markers of basic pathogenic variants of ischemic strokes in cerebral atherosclerosis. Annaly klinicheskoy i eksperimental’noy nevrologii = Annals of Clinical and Experimental Neurology. 2018; 12(4): 16–22 (In Russ.)).


https://doi.org/10.25692/acen.2018.4.2. EDN: HKATMT.


4. Ануфриев П.Л., Танашян М.М., Гулевская Т.С. с соавт. Особенности атеросклероза церебральных артерий и патоморфологии инфарктов головного мозга при сахарном диабете 2-го типа. Анналы клинической и экспериментальной неврологии. 2015; 9(3): 4–9. (Anufriev P.L., Tanashyan M.M., Gulevskaya T.S. et al. Features of atherosclerosis of the cerebral arteries and pathomorphology of cerebral infarctions in patients with type 2 diabetes mellitus. Annaly klinicheskoy i eksperimental’noy nevrologii = Annals of Clinical and Experimental Neurology. 2015; 9(3): 4–9 (In Russ.)).


https://doi.org/10.17816/psaic143. EDN: TGYJUU.


5. Танашян М.М., Антонова К.В., Лагода О.В., Шабалина А.А. Решенные и нерешенные вопросы цереброваскулярной патологии при сахарном диабете. Анналы клинической и экспериментальной неврологии. 2021; 15(3): 5–14. (Tanashyan М.М., Antonova K.V., Lagoda О.V., Shabalina А.А. Resolved and unresolved issues of cerebrovascular disease in diabetes mellitus. Annaly klinicheskoy i eksperimental’noy nevrologii = Annals of Clinical and Experimental Neurology. 2021; 15(3): 5–14 (In Russ.)).


https://doi.org/10.54101/acen.2021.3.1. EDN: CVCVOF.


6. Ehtewish H., Arredouani A., El-Agnaf O. Diagnostic, prognostic, and mechanistic biomarkers of diabetes mellitus-associated cognitive decline. Int J Mol Sci. 2022; 23(11): 6144.


https://doi.org/10.3390/ijms23116144. PMID: 35682821. PMCID: PMC9181591.


7. Swardfager W., MacIntosh B.J. Depression, type 2 diabetes, and poststroke cognitive impairment. Neurorehabil Neural Repair. 2017; 31(1): 48–55.


https://doi.org/10.1177/1545968316656054. PMID: 27364648.


8. Lee K., Chen J., Wang C. Association between diabetes mellitus and post-stroke cognitive impairment. J Diabetes Investig. 2023; 14(1): 6–11.


https://doi.org/10.1111/jdi.13914. PMID: 36181402. PMCID: PMC9807143.


9. Michaelidou M., Pappachan J.M., Jeeyavudeen M.S. Management of diabesity: Current concepts. World J Diabetes. 2023; 14(4): 396–411.


https://doi.org/10.4239/wjd.v14.i4.396. PMID: 37122433. PMCID: PMC10130896.


10. Zimmet P., Alberti K.G., Shaw J. Global and societal implications of the diabetes epidemic. Nature. 2001; 414(6865): 782–87.


https://doi.org/10.1038/414782a. PMID: 11742409.


11. Mosenzon O., Cheng A.Y., Rabinstein A.A., Sacco S. Diabetes and stroke: What are the connections? J Stroke. 2023; 25(1): 26–38.


https://doi.org/10.5853/jos.2022.02306. PMID: 36592968. PMCID: PMC9911852.


12. He C., Yang Z.G., Chu Z.G. et al. Carotid and cerebrovascular disease in symptomatic patients with type 2 diabetes: Assessment of prevalence and plaque morphology by dual-source computed tomography angiography. Cardiovasc Diabetol. 2010; 9: 91.


https://doi.org/10.1186/1475-2840-9-91. PMID: 21167061. PMCID: PMC3022609.


13. Танашян М.М., Лагода О.В., Антонова К.В. Цереброваскулярная патология и метаболический синдром. Монография. М.: АСТ 345. 2019; 376 с. (Tanashyan M.M., Lagoda O.V., Antonova K.V. Cerebrovascular pathology and metabolic syndrome. Monograph. Moscow: AST 345. 2019; 376 pp. (In Russ.)).


ISBN: 978-5-6041430-2-5. https://doi.org/10.33901/978-5-6041430-2-5-2019-1-370. EDN: SBMYLF.


14. Poznyak A., Grechko A.V., Poggio P. et al. The diabetes mellitus – atherosclerosis connection: The role of lipid and glucose metabolism and chronic inflammation. Int J Mol Sci. 2020; 21(5): 1835.


https://doi.org/10.3390/ijms21051835. PMID: 32155866. PMCID: PMC7084712.


15. Nedosugova L.V., Lankin V.Z., Balabolkin M.I. et al. Interrelation between compensation of carbohydrate metabolism and severity of manifestations of oxidative stress in type II diabetes mellitus. Bull Exp Biol Med. 2003; 136(2): 132–34.


https://doi.org/10.1023/a:1026302520288. PMID: 14631491.


16. Khan M.I., Ashfaq F., Alsayegh A.A. et al. Advanced glycation end product signaling and metabolic complications: Dietary approach. World J Diabetes. 2023; 14(7): 995–1012.


https://doi.org/10.4239/wjd.v14.i7.995. PMID: 37547584. PMCID: PMC10401445.


17. Wang P., Huang R., Lu S. et al. RAGE and AGEs in mild cognitive impairment of diabetic patients: A cross-sectional study. PLoS One. 2016; 11(1): e0145521.


https://doi.org/10.1371/journal.pone.0145521. PMID: 26745632. PMCID: PMC4706319.


18. Dhawan P., Vasishta S., Balakrishnan A., Joshi M.B. Mechanistic insights into glucose induced vascular epigenetic reprogramming in type 2 diabetes. Life Sci. 2022; 298: 120490.


https://doi.org/10.1016/j.lfs.2022.120490. PMID: 35331720.


19. Ramya C.M., Rajalakshmi R., Uma V., Bhanukumar M. Role of glycemic status and insulin resistance indices on cognition. Biomedicine. 2023; 43(2): 718–21.


https://doi.org/10.51248/.v43i02.2235.


20. Танашян М.М., Антонова К.В., Раскуражев А.А. с соавт. Цереброваскулярные заболевания и глюколипотоксичность. Анналы клинической и экспериментальной неврологии. 2020; 14(1): 17–24. (Tanashyan M.M., Antonova K.V., Raskurazhev A.A. et al. Cerebrovascular disorders and glucolipotoxicity. Annaly klinicheskoy i eksperimental’noy nevrologii = Annals of Clinical and Experimental Neurology. 2020. 14(1): 17–24 (In Russ.)).


https://doi.org/10.25692/ACEN.2020.1.2. EDN: BBQBEC.


21. Yang Y., Huang X., Wang Y. et al. The impact of triglyceride-glucose index on ischemic stroke: A systematic review and meta-analysis. Cardiovasc Diabetol. 2023; 22(1): 2.


https://doi.org/10.1186/s12933-022-01732-0. PMID: 36609319. PMCID: PMC9825038.


22. Sharif S., Van der Graaf Y., Cramer M.J. et al. Low-grade inflammation as a risk factor for cardiovascular events and all-cause mortality in patients with type 2 diabetes. Cardiovasc Diabetol. 2021; 20(1): 220.


https://doi.org/10.1186/s12933-021-01409-0. PMID: 34753497. PMCID: PMC8579639.


23. Procyk G., Czapla A., Jałocha K. et al. The role of galectin-3 in atrial fibrillation. J Mol Med (Berl). 2023; 101(12): 1481–92.


https://doi.org/10.1007/s00109-023-02378-5. PMID: 37773454. PMCID: PMC10698102.


24. Zaborska B., Sygitowicz G., Smarż K. Galectin-3 is related to right ventricular dysfunction in heart failure patients with reduced ejection fraction and may affect exercise capacity. Sci Rep. 2020; 10(1): 16682.


https://doi.org/10.1038/s41598-020-73634-8. PMID: 33028850. PMCID: PMC7542167.


25. Venkatraman A., Hardas S., Patel N. et al. Galectin-3: An emerging biomarker in stroke and cerebrovascular diseases. Eur J Neurol. 2018; 25(2): 238–46.


https://doi.org/10.1111/ene.13496. PMID: 29053903.


26. Gupta T., Kaur M., Shekhawat D. et al. Investigating the glucagon-like peptide-1 and its receptor in human brain: distribution of expression, functional implications, age-related changes and species specific characteristics. Basic Clin Neurosci. 2023; 14(3): 341–53.


https://doi.org/10.32598/bcn.2021.2554.2. PMID: 38077175. PMCID: PMC10700809.


27. Kong F., Wu T., Dai J. et al. Glucagon-like peptide 1 (GLP-1) receptor agonists in experimental Alzheimer’s disease models: A systematic review and meta-analysis of preclinical studies. Front Pharmacol. 2023; 14: 1205207.


https://doi.org/10.3389/fphar.2023.1205207. PMID: 37771725. PMCID: PMC10525376.


28. Horn J.W., Feng T., Mørkedal B. et al. Obesity and risk for first ischemic stroke depends on metabolic syndrome: The HUNT study. Stroke. 2021; 52(11): 3555–61.


https://doi.org/10.1161/strokeaha.120.033016. PMID: 34281375.


29. Романцова Т.И., Сыч Ю.П. Иммунометаболизм и метавоспаление при ожирении. Ожирение и метаболизм. 2019; 16(4): 3–17. (Romantsova T.I., Sych Yu.P. Immunometabolism and metainflammation in obesity. Ozhireniye i metabolizm = Obesity and Metabolism. 2019; 16(4): 3–17 (In Russ.)).


https://doi.org/10.14341/omet12218. EDN: GIFRWJ.


30. Maurizi G., Della Guardia L., Maurizi A., Poloni A. Adipocytes properties and crosstalk with immune system in obesity-related inflammation. J Cell Physiol. 2018; 233(1): 88–97.


https://doi.org/10.1002/jcp.25855. PMID: 28181253.


31. Sun J., Meng X., Huang H. et al. Higher visceral adiposity index and lipid accumulation product in relation to increased risk of atherosclerotic burden in community-dwelling older adults. Exp Gerontol. 2023; 174: 112115.


https://doi.org/10.1016/j.exger.2023.112115. PMID: 36758647.


32. Li R., Li Q., Cui M. et al. Visceral adiposity index, lipid accumulation product and intracranial atherosclerotic stenosis in middle-aged and elderly Chinese. Sci Rep. 2017; 7(1): 7951.


https://doi.org/10.1038/s41598-017-07811-7. PMID: 28801558. PMCID: PMC5554161.


33. Abdali M.R., Hamzah E.F., Neama E.D. et al. Investigation of the PON1(C>T rs705379) SNP and its correlation with physiological adiponectin levels in insulin resistance t2d patients induced by obesity. International Journal of Chemical and Biochemical Sciences. 2023; 23(1): 314–19.


34. Pezzino S., Luca T., Castorina M. et al. Role of perturbated hemostasis in MASLD and its correlation with adipokines. Life. 2024; 14(1): 93.


https://doi.org/10.3390/life14010093. PMID: 38255708. PMCID: PMC10820028.


35. Agbaedeng T.A., Iroga P.E., Rathnasekara V.M., Zacharia A.L. Adipokines and stroke: A systematic review and meta-analysis of disease risk and patient outcomes. Obes Rev. 2024: 25(4): e13684.


https://doi.org/10.1111/obr.13684. PMID: 38291816.


36. Arshad N., Lin T.S., Yahaya M.F. Metabolic syndrome and its effect on the brain: Possible mechanism. CNS Neurol Disord Drug Targets. 2018; 17(8): 595–603.


https://doi.org/10.2174/1871527317666180724143258. PMID: 30047340.


37. Davanzo G.G., Castro G., Monteiro L.B. et al. Obesity increases blood-brain barrier permeability and aggravates the mouse model of multiple sclerosis. Mult Scler Relat Disord. 2023; 72: 104605.


https://doi.org/10.1016/j.msard.2023.104605. PMID: 36907120.


38. Galley J.C., Singh S., Awata W.M.C. et al. Adipokines: Deciphering the cardiovascular signature of adipose tissue. Biochem Pharmacol. 2022; 206: 115324.


https://doi.org/10.1016/j.bcp.2022.115324. PMID: 36309078. PMCID: PMC10509780.


39. Opatrilova R., Caprnda M., Kubatka P. et al. Adipokines in neurovascular diseases. Biomed Pharmacother. 2018; 98: 424–32.


https://doi.org/10.1016/j.biopha.2017.12.074. PMID: 29278852.


40. Vliora M., Ravelli C., Grillo E. et al. The impact of adipokines on vascular networks in adipose tissue. Cytokine Growth Factor Rev. 2023; 69: 61–72.


https://doi.org/10.1016/j.cytogfr.2022.07.008. PMID: 35953434.


41. Shen M., Zhang M., Mao N. et al. Batokine in central nervous system diseases. Mol Neurobiol. 2023; 60(12): 7021–31.


https://doi.org/10.1007/s12035-023-03490-w. PMID: 37526894.


42. AlZaim I., Kalucka J. Batokine neuregulin 4 promotes atherosclerotic resolution. Nat Metab. 2022; 4(11): 1440–41.


https://doi.org/10.1038/s42255-022-00669-8. PMID: 36400934.


43. Вульф М.А., Сафиуллина Л.А., Газатова Н.Д. с соавт. Повышение нейрегулина-4 в крови связано с СД 2-го типа и гипертонической болезнью у больных ожирением. Российский иммунологический журнал. 2022; 25(4): 411–418. (Vulf M.A., Safiullina L.A., Gazatova N.D. et al. Increase of blood neuregulin 4 is associated with type 2 diabetes mellitus and hypertension in obese patients. Rossiyskiy immunologicheskiy zhurnal = Russian Journal of Immunology. 2022; 25(4): 411–418 (In Russ.)).


https://doi.org/10.46235/1028-7221-1207-IOB. EDN: HJXCOS.


44. Ha G., De Torres F., Arouche N. et al. GDF15 secreted by senescent endothelial cells improves vascular progenitor cell functions. PLoS One. 2019; 14(5): e0216602.


https://doi.org/10.1371/journal.pone.0216602. PMID: 31075112. PMCID: PMC6510423.


45. Vilahur G., Ben-Aicha S., Badimon L. New insights into the role of adipose tissue in thrombosis. Cardiovasc Res. 2017; 113(9): 1046–54.


https://doi.org/10.1093/cvr/cvx086. PMID: 28472252.


46. Ramírez-Carreto R.J., Rodríguez-Cortés Y.M., Torres-Guerrero H., Chavarría A. Possible implications of obesity-primed microglia that could contribute to stroke-associated damage. Cell Mol Neurobiol. 2023; 43(6): 2473–90.


https://doi.org/10.1007/s10571-023-01329-5. PMID: 36935429. PMCID: PMC10025068.


47. Gorska-Ciebiada M., Saryusz-Wolska M., Borkowska A. et al. Adhesion molecules and markers of systemic inflammation in elderly diabetic patients with mild cognitive impairment and depressive symptoms. Biomed Res Int. 2015; 2015: 826180.


https://doi.org/10.1155/2015/826180. PMID: 26167502. PMCID: PMC4488515.


48. Bi C., Fu Y., Li B. Brain-derived neurotrophic factor alleviates diabetes mellitus-accelerated atherosclerosis by promoting M2 polarization of macrophages through repressing the STAT3 pathway. Cell Signal. 2020; 70: 109569.


https://doi.org/10.1016/j.cellsig.2020.109569. PMID: 32061924.


49. Moosaie F., Mohammadi S., Saghazadeh A. et al. Brain-derived neurotrophic factor in diabetes mellitus: A systematic review and meta-analysis. PLoS One. 2023; 18(2): e0268816.


https://doi.org/10.1371/journal.pone.0268816. PMID: 36787304. PMCID: PMC9928073.


50. Bi J., Zhang J., Ren Y. et al. Irisin reverses intestinal epithelial barrier dysfunction during intestinal injury via binding to the integrin αVβ5 receptor. J Cell Mol Med. 2020; 24(1): 996–1009.


https://doi.org/10.1111/jcmm.14811. PMID: 31701659. PMCID: PMC6933384.


51. Cheng Z.B., Huang L., Xiao X. et al. Irisin in atherosclerosis. Clin Chim Acta. 2021; 522: 158–66.


https://doi.org/10.1016/j.cca.2021.08.022. PMID: 34425103.


52. Pinho-Jr. J.D.S., Camacho F.A., Cavararo C.D.S. et al. Irisin and cardiometabolic disorders in obesity: A systematic review. Int J Inflam. 2023; 2023: 5810157.


https://doi.org/10.1155/2023/5810157. PMID: 37900979. PMCID: PMC10602702.


About the Autors


Marine M. Tanashyan, MD, Dr. Sci. (Medicine), professor, corresponding member of RAS, deputy director for scientific work, head of the 1st Neurological Department, Scientific Center of Neurology. Address: 125367, Moscow, 80 Volokolamskoe Highway.
E-mail: mtanashyan@neurology.ru
ORCID: https://orcid.org/0000-0002-5883-8119. Researcher ID: F-8483-2014. Scopus Author ID: 6506228066. eLibrary SPIN: 7191-1163
Ksenia V. Antonova, MD, Dr. Sci. (Medicine), leading researcher, endocrinologist of Scientific Center of Neurology. Address: 125367, Moscow, 80 Volokolamskoe Highway.
E-mail: kseniya.antonova@mail.ru
ORCID: https://orcid.org/0000-0003-2373-2231. Researcher ID: J-9971-2016. Scopus Author ID: 7004672742. eLibrary SPIN: 7737-4712
Nikita E. Spryshkov, MD, 1st year postgraduate student, neurologist at of Scientific Center of Neurology. Address: 125367, Moscow, 80 Volokolamskoe Highway.
E-mail: nikita_spryshkov@mail.ru
ORCID: https://orcid.org/0000-0002-2934-5462. eLibrary SPIN: 4604-7589
Anastasia A. Panina, MD, 1st year postgraduate student, neurologist at of Scientific Center of Neurology. Address: 125367, Moscow, 80 Volokolamskoe Highway.
E-mail: nastena.panina.98@mail.ru
ORCID: https://orcid.org/0000-0002-8652-2947


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