Association of serum elabela levels with carotid artery stenosis in patients with non-cardioembolic ischemic stroke
Abstract
Aim: Elabela (ELA) is a peptide of the apelinergic system and is known to play a role in endothelial homeostasis and vascular pathobiology. In this study, the relationship between carotid artery stenosis, which is the main culprit, and ELA level in patients with non-cardioembolic ischemic stroke was investigated. Materials & methods: Cross-sectional observation included two groups of 40 patients with critical carotid artery stenosis and 40 patients with age–sex matched noncritical carotid artery stenosis. Results: ELA levels were significantly higher in the noncritical stenosis group. ELA had a significantly moderate negative correlation with the carotid score (r = -0.334, p = 0.003), maximal carotid plaque length (r = -0.413, p < 0.001) and degree of stenosis (r = -0.397, p < 0.001). Conclusions: There is a significant inverse correlation between critical carotid artery disease and ELA level in patients with non-cardioembolic ischemic stroke.
References
- 1. . Global variation in stroke burden and mortality: estimates from monitoring, surveillance, and modelling. Lancet Neurol. 8, 345–354 (2009).
- 2. A computerized algorithm for etiologic classification of ischemic stroke: the causative classification of stroke system. Stroke 38, 2979–2984 (2007).
- 3. . National Institute for Health and Care Excellence NG128 stroke and transient ischaemic attack in over 16s: diagnosis and initial management. British J. Cardiac Nursing 15, 1–5 (2020).
- 4. Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler. Thromb. Vasc. Biol. 20, 1262–1275 (2000).
- 5. Elabela: a hormone essential for heart development signals via the apelin receptor. Dev. Cell 27, 672–680 (2013).
- 6. Elabela/toddler is an endogenous agonist of the apelin apj receptor in the adult cardiovascular system, and exogenous administration of the peptide compensates for the down-regulation of its expression in pulmonary arterial hypertension. Circulation 135, 1160–1173 (2017).
- 7. Elabela may regulate SIRT3-mediated inhibition of oxidative stress through foxo3a deacetylation preventing diabetic-induced myocardial injury. J. Cell. Mol. Med. 25, 323–332 (2021).
- 8. Elabela improves endothelial cell function via the ELA-APJ axis by activating the PI3K/Akt signalling pathway in HUVECs and EA.hy926 cells. Clin. Exp. Pharmacol. Physiol. 47, 1953–1964 (2020).
- 9. Lower plasma elabela levels in hypertensive patients with heart failure predict the occurrence of major adverse cardiac events: a preliminary study. Front Cardiovasc. Med. 8, 638468 (2021).
- 10. Plasma levels of elabela are associated with coronary angiographic severity in patients with acute coronary syndrome. J. Geriatr. Cardiol. 17, 674–679 (2020).
- 11. . Elabela as a novel marker: well-correlated with WIfI amputation risk score in lower extremity arterial disease patients. Anatol. J. Cardiol. 25, 330–337 (2021).
- 12. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N. Engl. J. Med. 325, 445–453 (1991).
- 13. Additive prognostic value of carotid plaque score to enhance the age, creatinine, and ejection fraction score in patients with acute coronary syndrome. J. Atheroscler. Thromb. 25, 709–719 (2018).
- 14. Prevalence and predictors of concomitant carotid and coronary artery atherosclerotic disease. J. Am. Coll. Cardiol. 57, 779–783 (2011).
- 15. Association between genetic polymorphisms and carotid atherosclerosis in patients treated with radiotherapy for nasopharyngeal carcinoma. Radiat. Oncol. 10, 39 (2015).
- 16. The independent and incremental value of ultrasound carotid plaque length to predict the presence and severity of coronary artery disease: analysis from the carotid plaque length prospective registry. Eur. Heart J. Cardiovasc. Imaging 21, 389–396 (2020).
- 17. Modulation of the apelin/APJ system in heart failure and atherosclerosis in man. Br. J. Pharmacol. 160, 1785–1795 (2010).
- 18. . Immunocytochemical localization of the endogenous vasoactive peptide apelin to human vascular and endocardial endothelial cells. Regul. Pept. 118, 119–125 (2004).
- 19. Apelin, the ligand for the endothelial G-protein-coupled receptor, APJ, is a potent angiogenic factor required for normal vascular development of the frog embryo. Dev. Biol. 296, 177–189 (2006).
- 20. Apelin directs endothelial cell differentiation and vascular repair following immune-mediated injury. J. Clin. Invest. 130, 94–107 (2020).
- 21. Apelin protects against abdominal aortic aneurysm and the therapeutic role of neutral endopeptidase resistant apelin analogs. Proc. Natl Acad. Sci. USA 116, 13006–13015 (2019).
- 22. Plasma level of apelin and carotid atherosclerosis in maintenance hemodialysis patients. Chinese 42, 617–622 (2017).
- 23. Relationship of apelin, procalcitonin, and fetuin-A concentrations with carotid intima-media thickness in acromegaly. Ann. Clin. Biochem. 52, 456–461 (2015).
- 24. Apelin concentrations are associated with altered atherosclerotic plaque stability mediator levels and atherosclerosis in rheumatoid arthritis. Atherosclerosis 256, 75–81 (2017).
- 25. . Apelin: a potential marker of coronary artery stenosis and atherosclerotic plaque stability in ACS patients. Int. Heart J. 55, 204–212 (2014).
- 26. Serum apelin: a new marker of early atherosclerosis in children with type 1 diabetes mellitus. Open Access Maced. J. Med. Sci. 6, 613–617 (2018).
- 27. . Endothelial dysfunction: a marker of atherosclerotic risk. Arterioscler. Thromb. Vasc. Biol. 23, 168–175 (2003).
- 28. Greater reductions in plasma aldosterone with aliskiren in hypertensive patients with higher soluble (pro)renin receptor level. Hypertens. Res. 41, 435–444 (2018).
- 29. Elabela antagonizes intrarenal renin-angiotensin system to lower blood pressure and protects against renal injury. Am. J. Physiol. Renal Physiol. 318, 1122–1135 (2020).
- 30. Elabela plasma concentrations are increased in women with late-onset pre-eclampsia. J. Matern. Fetal Neonatal Med. 33, 5–15 (2020).
- 31. Apela Regulates Fluid Homeostasis by Binding to the APJ Receptor to Activate Gi Signaling. J. Biol. Chem. 290, 18261–18268 (2015).
- 32. . The apelin/APJ system in the regulation of vascular tone: friend or foe? J. Biochem. 169, 383–386 (2021).
- 33. Apelin/APJ system: a potential therapeutic target for endothelial dysfunction-related diseases. J. Cell. Physiol. 234, 12149–12160 (2019).
- 34. . The elabela in hypertension, cardiovascular disease, renal disease, and pre-eclampsia: an update. J. Hypertens. 39, 12–22 (2021).
- 35. . Emerging role of the apelin system in cardiovascular homeostasis. Biomark. Med. 1, 37–43 (2007).