Uloga neurotrofina u akutnom koronarnom sindromu prognostička i dijagnostička vrednost novih biomarkera
Ključne reči:
akutni koronarni sindrom, neurotrofini, BDNF, NGF, biomarkeri, prognoza, dijagnoza.
Sažetak
Akutni koronarni sindrom (AKS) predstavlja vodeći uzrok morbiditeta i mortaliteta širom sveta. Iako su postojeći dijagnostički i prognostički biomarkeri unapredili lečenje pacijenata, i dalje postoji potreba za novim, specifičnijim markerima koji bi omogućili precizniju stratifikaciju rizika i individualni pristup u lečenju. Neurotrofini predstavljaju porodicu proteina esencijalnih za preživljavanje i funkciju neurona. Poslednjih godinna sve više se prepoznaje njihova uloga u bolestima kardiovaskularnog sistema. Cilj ovog revijalnog rada je da predstavi aktuelna saznanja o ulozi neurotrofina, prvenstveno BDNF-a i NGF-a, u patofiziologiji AKS-a, kao i da proceni njihov potencijal kao novih dijagnostičkih i prognostičkih biomarkera. Analizirane studije ukazuju na značajne promene u nivoima neurotrofina tokom AKS-a, povezujući ih sa ishemijom, reperfuzionom povredom, inflamacijom i remodelovanjem miokarda. Postoje dokazi da povišeni ili sniženi nivoi određenih neurotrofina mogu predvideti kratkoročne i dugoročne ishode kod pacijenata sa AKS-om. Dalja istraživanja, posebno velike multicentrične studije, neophodna su kako bi se potvrdila vrednost određivanja neurotrofina u AKS kao značajnog biomarkera u praksi.
Reference
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28. Liu Y, Sun L, Huan Y, Zhao H, Deng J. Application of bFGF and BDNF to improve angiogenesis and cardiac function. J Surg Res. 2006 Dec;136(1):85–91.
29. Ovsyannikov Y, Efremova V, Kozina A, Pakhomova A, Elgarte V, Orlova T, et al. Nerve growth factor and post-infarction cardiac remodeling. Acta Biomed Sci. 2021;6(5):34–41.
30. Lafuse WP, Wozniak DJ, Rajaram MVS. Role of cardiac macrophages on cardiac inflammation, fibrosis and tissue repair. Cells. 2020;10(1):51.
31. Wang T, Wang X, Han S, Sun Y, Wang L, Huang Y. Nerve growth factor promotes myocardial fibrosis after myocardial infarction via activation of cardiac fibroblasts. Int J Mol Med. 2016 Oct;38(4):1199–208.
32. Xiong Q, Li M, Wu Q, Xu W, Chen Q. Low serum brain-derived neurotrophic factor levels predict adverse prognosis in patients with ST-elevation myocardial infarction. J Cardiovasc Med (Hagerstown). 2018;19(11):625–30.
33. Li JN, Luo RY, Luo C, Hu ZL, Zha AH, Shen WY, et al. Brain-Derived Neurotrophic Factor Precursor Contributes to a Proinflammatory Program in Monocytes/Macrophages After Acute Myocardial Infarction. J Am Heart Assoc. 2023 Mar 21;12(6):e028198.
34. Tsuboi A, Sakagami T, Yoshimoto T, Niki M, Sawa T, Kurihara T, et al. Plasma brain-derived neurotrophic factor levels predict adverse cardiac events in patients with acute myocardial infarction. Heart Vessels. 2020 Jan;35(1):15–22.
35. Zhang Y, Li Y, Wang H, Deng J, Zhang Z, Liu L, et al. Decreased serum brain-derived neurotrophic factor levels in patients with acute coronary syndrome: a meta-analysis. Biomed Pharmacother. 2017;93:928–35.
36. Polanco JC, Al-Hassani A, Kim MK, Lee J, Kim HJ, Jang S, et al. Current approaches for the quantification of neurotrophins. J Immunol Methods. 2020;483:112814.
2. Thygesen K, Alpert JS, Jaffe AS, Chaitman BP, Bax JJ, Morrow DA, et al. Fourth Universal Definition of Myocardial Infarction (2018). J Am Coll Cardiol. 2018;72(18):2231–64.
3. Byrne RA, Rossello X, Coughlan JJ, Barbato E, Berry C, Chieffo A, et al. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J. 2023;44(38):3720–826.
4. Reichardt LF. Neurotrophin-regulated signalling pathways. Philos Trans R Soc Lond B Biol Sci. 2006;361(1473):1545–65.
5. Lichtman JH, Froelicher ES, Blumenthal JA, Carney RM, Doering LV, Packer M, et al. Depression as a risk factor for poor prognosis among patients with acute coronary syndrome: systematic review and recommendations. Circulation. 2014;129(12):1350-69.
6. Duman RS, Monteggia LM. A neurotrophic model of stress-related mood disorders. Biol Psychiatry. 2006;59(12):1116-27.
7. Mitrovic M, Selakovic D, Jovicic N, Ljujic B, Rosic G. BDNF/proBDNF Interplay in the Mediation of Neuronal Apoptotic Mechanisms in Neurodegenerative Diseases. Int J Mol Sci. 2025;26(10):4926. doi:10.3390/ijms26104926
8. Kotecha D, Marber MS. Neurotrophins in the heart: a new therapeutic target?. Cardiovasc Res. 2012;94(2):261-9.
9. Emanueli C, Spiga S, Stasi MA, Gnecchi M, Angeloni D, Stanta G, et al. Neurotrophic factors in the heart: a new therapeutic frontier. Circ Res. 2007;100(11):1591-601.
10. Wang T, Chen L, Zhu T, Han P, Cui W. Neurotrophins and their receptors in cardiovascular diseases. Biomed Pharmacother. 2022;145:112440.
11. Chao MV. Neurotrophins and their receptors: a convergence point for many signalling pathways. Nat Rev Neurosci. 2003;4(10):769–79.
12. Dechant G, Barde YA. The neurotrophin receptor p75NTR: a tale of two actions. Trends Neurosci. 2002;25(11):597–603.
13. Hang PZ, Zhu H, Li PF, Liu J, Ge FQ, Zhao J, et al. The Emerging Role of BDNF/TrkB Signaling in Cardiovascular Diseases. Life (Basel). 2021;11(1):70.
14. Itoh Y, Mochizuki N. Neurotrophins in the cardiovascular system. J Pharmacol Sci. 2011;117(2):83–91.
15. Feng N, Huke S, Zhu G, Tocchetti CG, Shi S, Aiba T, et al. Constitutive BDNF/TrkB signaling is required for normal cardiac contraction and relaxation. Proc Natl Acad Sci U S A. 2015 Feb 10;112(6):1880–5.
16. Di Lascio V, Castelli M, Rosti V, Pela G, Pasi F. Nerve growth factor in ischemic heart disease. J Cardiovasc Transl Res. 2012;5(6):859–66.
17. Söderdahl T, Jernberg T, Viberg T, Svensson P, Lindahl B, Juhlin C. High levels of nerve growth factor are associated with adverse prognosis in patients with acute coronary syndromes. Heart. 2012;98(23):1717–22.
18. Mallat Z, Philip I, Chvatchko Y, Leseche G, Tedgui A. Nerve growth factor expression in human ischemic heart disease. Circulation. 2001;104(22):2667–72.
19. Manni L, Lundeberg T, Vigneti D. Brain-derived neurotrophic factor (BDNF) in cardiovascular diseases: a review. J Cardiovasc Transl Res. 2014;7(2):167–75.
20. Gao F, Zhu T, Li N, Ma X, Sun M, Wu M. Brain-derived neurotrophic factor protects cardiomyocytes against ischemia-reperfusion injury through PI3K/Akt pathway. Mol Cell Biochem. 2015;407(1-2):189–95.
21. Cai B, Luo X, Li X, Liu L, Hu W, Feng Y, et al. Exogenous brain-derived neurotrophic factor improves cardiac function after myocardial infarction in rats. J Card Fail. 2015;21(7):601–10.
22. Hiltunen JO, Laurikainen A, Vakeva A, Meri S, Saarma M. Nerve growth factor and brain-derived neurotrophic factor mRNAs are regulated in distinct cell populations of rat heart after ischaemia and reperfusion. J Pathol. 2001;194(2):247–53.
23. Ieda M, Fukuda K, Hisaka Y, Kimura K, Kawaguchi H, Fujita J, et al. Endothelin-1 regulates cardiac sympathetic innervation in the rodent heart by controlling nerve growth factor expression. J Clin Invest. 2004;113(6):876–84.
24. Montone RA, Camilli M, Del Buono MG, Russo M, Rinaldi R, Canonico F, et al. Brain-derived neurotrophic factor in patients with acute coronary syndrome. Transl Res. 2021 May;231:39–54.
25. Kerekes G, Szabo E, Szabo Z, Horvath T, Toth I, Keresztes K, et al. Serum brain-derived neurotrophic factor levels in acute myocardial infarction patients. J Clin Lab Anal. 2017;31(2):e22026.
26. Shen WY, Luo C, Hurtado P, Hurtado-Perez E, Luo RY, Hu ZL, et al. The regulatory role of ProBDNF in monocyte function: implications in Stanford type-A aortic dissection disease. FASEB J. 2020;34(2):2541–53.
27. Chrysohoou C, Vrotsou K, Pitsavos C, Skoumas I, Papageorgiou N, Tousoulis D, et al. Neurotrophins in acute coronary syndromes: A systematic review. Int J Cardiol. 2018 Jan 1;250:111–6.
28. Liu Y, Sun L, Huan Y, Zhao H, Deng J. Application of bFGF and BDNF to improve angiogenesis and cardiac function. J Surg Res. 2006 Dec;136(1):85–91.
29. Ovsyannikov Y, Efremova V, Kozina A, Pakhomova A, Elgarte V, Orlova T, et al. Nerve growth factor and post-infarction cardiac remodeling. Acta Biomed Sci. 2021;6(5):34–41.
30. Lafuse WP, Wozniak DJ, Rajaram MVS. Role of cardiac macrophages on cardiac inflammation, fibrosis and tissue repair. Cells. 2020;10(1):51.
31. Wang T, Wang X, Han S, Sun Y, Wang L, Huang Y. Nerve growth factor promotes myocardial fibrosis after myocardial infarction via activation of cardiac fibroblasts. Int J Mol Med. 2016 Oct;38(4):1199–208.
32. Xiong Q, Li M, Wu Q, Xu W, Chen Q. Low serum brain-derived neurotrophic factor levels predict adverse prognosis in patients with ST-elevation myocardial infarction. J Cardiovasc Med (Hagerstown). 2018;19(11):625–30.
33. Li JN, Luo RY, Luo C, Hu ZL, Zha AH, Shen WY, et al. Brain-Derived Neurotrophic Factor Precursor Contributes to a Proinflammatory Program in Monocytes/Macrophages After Acute Myocardial Infarction. J Am Heart Assoc. 2023 Mar 21;12(6):e028198.
34. Tsuboi A, Sakagami T, Yoshimoto T, Niki M, Sawa T, Kurihara T, et al. Plasma brain-derived neurotrophic factor levels predict adverse cardiac events in patients with acute myocardial infarction. Heart Vessels. 2020 Jan;35(1):15–22.
35. Zhang Y, Li Y, Wang H, Deng J, Zhang Z, Liu L, et al. Decreased serum brain-derived neurotrophic factor levels in patients with acute coronary syndrome: a meta-analysis. Biomed Pharmacother. 2017;93:928–35.
36. Polanco JC, Al-Hassani A, Kim MK, Lee J, Kim HJ, Jang S, et al. Current approaches for the quantification of neurotrophins. J Immunol Methods. 2020;483:112814.
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2025/12/30
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