Early Administration of Apelin Could Prevent Heart Failure Following Myocardial Injury; A Systematic Review and Meta-Analysis
Archives of Academic Emergency Medicine,
Vol. 13 No. 1 (2025),
6 September 2025
,
Page e4
https://doi.org/10.22037/aaem.v13i1.2414
Abstract
Introduction: Heart failure (HF) is a prevalent and advancing cardiovascular disorder that impacts 1-2% of the worldwide population, particularly the elderly. Studies indicate that the intravenous administration of apelin may yield advantageous effects in preventing heart failure subsequent to myocardial injury. This meta-analysis aimed to assess the effects of exogenous apelin administration on heart failure in animal models, in light of the lack of a definitive consensus on the matter.
Method: An extensive search was performed in the Medline (via PubMed), Web of Science, Embase, and Scopus databases till the end of January 2024. Two independent reviewers screened and summarized the relevant articles. Outcomes related to cardiac function, including ejection fraction (EF), maximum and minimum rate of left ventricle systolic pressure (+dp/dt and –dp/dt, respectively), heart rate, left ventricular end-diastolic pressure (LVEDP), and left ventricular systolic pressure (LVSP) were assessed. Findings were reported as a pooled standardized mean difference (SMD) with a 95% confidence interval (95% CI).
Results: 12 studies were included. Pooled analysis demonstrated that early treatment with apelin following myocardial injury significantly increases +dp/dt (SMD = 2.36; 95% CI: 1.58 to 3.15; p < 0.001) and decreases -dp/dt (SMD = -3.31; 95% CI: -4.46 to -2.17; p < 0.001). Furthermore, the administration of apelin resulted in a significant increase in EF (SMD = 0.79; 95% CI: 0.15 to 1.44; p = 0.02) and LVSP (SMD = 2.09; 95% CI: 0.82 to 3.36; p < 0.001), while it led to a decrease in LVEDP in the animals (SMD = -1.85; 95% CI: -2.81 to -0.88; p < 0.001). Noteworthy, apelin treatment was shown to have no significant influence on the heart rate of the animals (SMD = -0.12; 95% CI: -0.82 to -0.58; p = 0.73).
Conclusion: The current study demonstrated that the early administration of apelin has the potential to improve cardiac function and mitigate the onset of heart failure subsequent to myocardial injury. Further, in vivo research is essential to lay the groundwork for the integration of apelin into clinical practice.
- Apelin
- Myocardial Ischemia reperfusion injury
- Acute Myocardial Infarction
- acute heart failure
How to Cite
References
Garg R, Packer M, Pitt B, Yusuf S. Heart failure in the 1990s: evolution of a major public health problem in cardiovascular medicine. J Am Coll Cardiol. 1993;22(4 Suppl A):3a-5a.
El Amrousy D, El-Mahdy H. Prognostic Value of Serum Apelin Level in Children with Heart Failure Secondary to Congenital Heart Disease. Pediatr Cardiol. 2018;39(6):1188-93.
Aalbers J. New ESC heart failure guidelines with South African expert comment. Cardiovasc J Afr. 2012;23(5):295-6.
Haldeman GA, Croft JB, Giles WH, Rashidee A. Hospitalization of patients with heart failure: National Hospital Discharge Survey, 1985 to 1995. Am Heart J. 1999;137(2):352-60.
Parikh VN, Liu J, Shang C, Woods C, Chang AC, Zhao M, et al. Apelin and APJ orchestrate complex tissue-specific control of cardiomyocyte hypertrophy and contractility in the hypertrophy-heart failure transition. Am J Physiol Heart Circ Physiol. 2018;315(2):H348-h56.
Cox CM, D'Agostino SL, Miller MK, Heimark RL, Krieg PA. 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. 2006;296(1):177-89.
Ma Y, Yue Y, Ma Y, Zhang Q, Zhou Q, Song Y, et al. Structural Basis for Apelin Control of the Human Apelin Receptor. Structure. 2017;25(6):858-66.e4.
Mohr-Sasson A, Chayo J, Bart Y, Meyer R, Sivan E, Mazaki-Tovi S, et al. Laboratory characteristics of pregnant compared to non-pregnant women infected with SARS-CoV-2. Archives of Gynecology and Obstetrics. 2020;302(3):629-34.
Chen L, Li Q, Zheng D, Jiang H, Wei Y, Zou L, et al. Clinical characteristics of pregnant women with Covid-19 in Wuhan, China. New England Journal of Medicine. 2020;382(25):e100.
Wang Z, Wang Z, Xiong G. Clinical characteristics and laboratory results of pregnant women with COVID‐19 in Wuhan, China. International Journal of Gynecology & Obstetrics. 2020;150(3):312-7.
Guan W-j, Ni Z-y, Hu Y, Liang W-h, Ou C-q, He J-x, et al. Clinical characteristics of coronavirus disease 2019 in China. New England journal of medicine. 2020;382(18):1708-20.
Kleinz MJ, Baxter GFJRp. Apelin reduces myocardial reperfusion injury independently of PI3K/Akt and P70S6 kinase. 2008;146(1-3):271-7.
Goidescu CM, Vida-Simiti LA. The Apelin-APJ System in the Evolution of Heart Failure. Clujul Med. 2015;88(1):3-8.
Japp AG, Newby DE. The apelin-APJ system in heart failure: pathophysiologic relevance and therapeutic potential. Biochem Pharmacol. 2008;75(10):1882-92.
Ouyang Q, You T, Guo J, Xu R, Guo Q, Lin J, et al. Effects of Apelin on Left Ventricular-Arterial Coupling and Mechanical Efficiency in Rats with Ischemic Heart Failure. Dis Markers. 2019;2019:4823156.
Folino A, Montarolo PG, Samaja M, Rastaldo R. Effects of apelin on the cardiovascular system. Heart Fail Rev. 2015;20(4):505-18.
Chen MM, Ashley EA, Deng DX, Tsalenko A, Deng A, Tabibiazar R, et al. Novel role for the potent endogenous inotrope apelin in human cardiac dysfunction. Circulation. 2003;108(12):1432-9.
Ashley EA, Powers J, Chen M, Kundu R, Finsterbach T, Caffarelli A, et al. The endogenous peptide apelin potently improves cardiac contractility and reduces cardiac loading in vivo. Cardiovasc Res. 2005;65(1):73-82.
Farkasfalvi K, Stagg MA, Coppen SR, Siedlecka U, Lee J, Soppa GK, et al. Direct effects of apelin on cardiomyocyte contractility and electrophysiology. Biochem Biophys Res Commun. 2007;357(4):889-95.
Ferdinal F, Limanan D, Rini RD, Alexsandro R, Helmi R. Elevated Levels of Apelin-36 in Heart Failure Due to Chronic Systemic Hypoxia. Int J Angiol. 2019;28(3):194-9.
Sato T, Suzuki T, Watanabe H, Kadowaki A, Fukamizu A, Liu PP, et al. Apelin is a positive regulator of ACE2 in failing hearts. 2013;123(12):5203-11.
Jia Y-X, Pan C-S, Zhang J, Geng B, Zhao J, Gerns H, et al. Apelin protects myocardial injury induced by isoproterenol in rats. 2006;133(1-3):147-54.
Hooijmans CR, Rovers MM, de Vries RB, Leenaars M, Ritskes-Hoitinga M, Langendam MW. SYRCLE's risk of bias tool for animal studies. BMC Med Res Methodol. 2014;14:43.
Doleman B, Freeman SC, Lund JN, Williams JP, Sutton AJJRSM. Funnel plots may show asymmetry in the absence of publication bias with continuous outcomes dependent on baseline risk: presentation of a new publication bias test. 2020;11(4):522-34.
Berry MF, Pirolli TJ, Jayasankar V, Burdick J, Morine KJ, Gardner TJ, et al. Apelin has in vivo inotropic effects on normal and failing hearts. Circulation. 2004;110(11 Suppl 1):Ii187-93.
Jia YX, Pan CS, Zhang J, Geng B, Zhao J, Gerns H, et al. Apelin protects myocardial injury induced by isoproterenol in rats. Regul Pept. 2006;133(1-3):147-54.
Pang H, Han B, Yu T, Zong Z. Effect of apelin on the cardiac hemodynamics in hypertensive rats with heart failure. Int J Mol Med. 2014;34(3):756-64.
Li L, Zeng H, Chen JX. Apelin-13 increases myocardial progenitor cells and improves repair postmyocardial infarction. Am J Physiol Heart Circ Physiol. 2012;303(5):H605-18.
Li Y, Lu H, Xu W, Shang Y, Zhao C, Wang Y, et al. Apelin ameliorated acute heart failure via inhibiting endoplasmic reticulum stress in rabbits. Amino Acids. 2021;53(3):417-27.
Sato T, Suzuki T, Watanabe H, Kadowaki A, Fukamizu A, Liu PP, et al. Apelin is a positive regulator of ACE2 in failing hearts. J Clin Invest. 2013;123(12):5203-11.
Soltani Hekmat A, Javanmardi K, Tavassoli A, Gholampour Y. Angiotensin (1-7) and Apelin co-therapy: New strategy for heart failure treatment of rats. Anatol J Cardiol. 2020;23(4):209-17.
Zhang X, Hu W, Feng F, Xu J, Wu F. Apelin-13 protects against myocardial infarction-induced myocardial fibrosis. Mol Med Rep. 2016;13(6):5262-8.
Zhong S, Guo H, Wang H, Xing D, Lu T, Yang J, et al. Apelin-13 alleviated cardiac fibrosis via inhibiting the PI3K/Akt pathway to attenuate oxidative stress in rats with myocardial infarction-induced heart failure. Biosci Rep. 2020;40(4).
Chung WJ, Cho A, Byun K, Moon J, Ge X, Seo HS, et al. Apelin-13 infusion salvages the peri-infarct region to preserve cardiac function after severe myocardial injury. Int J Cardiol. 2016;222:361-7.
Azizi Y, Faghihi M, Imani A, Roghani M, Zekri A, Mobasheri MB, et al. Post-infarct treatment with [Pyr(1)]apelin-13 improves myocardial function by increasing neovascularization and overexpression of angiogenic growth factors in rats. Eur J Pharmacol. 2015;761:101-8.
Foussal C, Lairez O, Calise D, Pathak A, Guilbeau-Frugier C, Valet P, et al. Activation of catalase by apelin prevents oxidative stress-linked cardiac hypertrophy. FEBS Lett. 2010;584(11):2363-70.
Ronkainen VP, Ronkainen JJ, Hänninen SL, Leskinen H, Ruas JL, Pereira T, et al. Hypoxia inducible factor regulates the cardiac expression and secretion of apelin. Faseb j. 2007;21(8):1821-30.
Kleinz MJ, Baxter GF. Apelin reduces myocardial reperfusion injury independently of PI3K/Akt and P70S6 kinase. Regul Pept. 2008;146(1-3):271-7.
Yang P, Maguire JJ, Davenport AP. Apelin, Elabela/Toddler, and biased agonists as novel therapeutic agents in the cardiovascular system. Trends Pharmacol Sci. 2015;36(9):560-7.
Dai T, Ramirez-Correa G, Gao WD. Apelin increases contractility in failing cardiac muscle. Eur J Pharmacol. 2006;553(1-3):222-8.
Atluri P, Morine KJ, Liao GP, Panlilio CM, Berry MF, Hsu VM, et al. Ischemic heart failure enhances endogenous myocardial apelin and APJ receptor expression. Cell Mol Biol Lett. 2007;12(1):127-38.
Rozwadowski J, Borodzicz-Jażdżyk S, Czarzasta K, Cudnoch-Jędrzejewska A. A Review of the Roles of Apelin and ELABELA Peptide Ligands in Cardiovascular Disease, Including Heart Failure and Hypertension. Med Sci Monit. 2022;28:e938112.
Yao F, Modgil A, Zhang Q, Pingili A, Singh N, O'Rourke ST, et al. Pressor effect of apelin-13 in the rostral ventrolateral medulla: role of NAD(P)H oxidase-derived superoxide. J Pharmacol Exp Ther. 2011;336(2):372-80.
Cheng X, Cheng XS, Pang CC. Venous dilator effect of apelin, an endogenous peptide ligand for the orphan APJ receptor, in conscious rats. Eur J Pharmacol. 2003;470(3):171-5.
- Abstract Viewed: 646 times
- pdf Downloaded: 1678 times
Download Statastics
Make a Submission
SJR
COPE
