The Effect of Interval Training Exercise on the Serum Level of Apelin-17 and Vascular Blood Flow Improvement in Patients with Heart Failure

Document Type : Original Article


1 PhD student, Department of Physical Education & Sports Sciences, Aliabad Katoul Branch, Islamic Azad University, Aliabad Katoul, Iran.

2 Assistant Professor of exercise physiology, Department of Physical Education & Sports Sciences, Aliabad Katoul Branch, Islamic Azad University, Aliabad Katoul, Iran.

3 Assistant Professor of exercise physiology, Department of Physical Education and Sports Science, Abadan Branch, Islamic Azad University, Abadan, Iran.


Background and Objectives Chronic hypertension causes structural and functional changes in the heart, ultimately leading to heart failure (HF), which further increases mortality. The aim of the present study was to examine the effect of intermittent aerobic exercise on the serum level of Apelin-17 and factors related to blood pressure in patients with HF. Subjects and Methods In this quasi-experimental study, 20 men with HF were selected based on the inclusion criteria and were randomly divided into exercise and control groups. The exercise program included interval aerobic training exercise that involved three sessions per week continued for eight weeks. Fasting blood samples and physiological variables were measured 48 hours before and after the intervention. Results After eight weeks of training, there was a significant increase in the levels of Apelin-17 (P = 0.039), Ang I (P = 0.005) and FMD (P = 0.008). A significant decrease in the levels of Ang II (P < 0.001) and SBP (P < 0.001) was observed, but no significant difference was found in the values of ACE-2 (P = 0.234) and DBP (P = 0.363). Conclusion According to the results, it can be stated that one of the adaptations of exercise that improves blood flow and lowers blood pressure in patients with HF is increasing the level of Apelin-17 in these patients.


Main Subjects

[1] Oh GC, Cho HJ. Blood pressure and heart failure. Clinical hypertension. 2020 Dec;26:1-8[Link].
[2] Jing MY, Li XY, Hao XY, Song GM. The impact of inspiratory muscle training on exercise capacity and inspiratory muscle strength in heart failure patients: a meta-analysis. TMR Non-drug Therapy. 2019 Dec 6;2(4):117-26[Link].
[3] Khoury EE, Kinaneh S, Aronson D, Amir O, Ghanim D, Volinsky N, Azzam Z, Abassi Z. Natriuretic peptides system in the pulmonary tissue of rats with heart failure: potential involvement in lung edema and inflammation. Oncotarget. 2018 Apr 4;9(31):21715.[ 10.18632/onc otarget.24922] [PMID]
[4] Kannel WB, D'Agostino RB, Silbershatz H, Belanger AJ, Wilson PW, Levy D. Profile for estimating risk of heart failure. Archives of internal medicine. 1999 Jun 14;159(11):1197-204. [10.1001/archinte.159.11.1197 ] [PMID]
[5] Dyck GJ, Raj P, Zieroth S, Dyck JR, Ezekowitz JA. The effects of resveratrol in patients with cardiovascular disease and heart failure: a narrative review. International journal of molecular sciences. 2019 Feb 19;20(4):904. [10.3390/ijms20040904 ] [PMID]
[6] Mansouri A, Baraz S, Elahi N, Miladinia M, Malehi AS. The Status of Quality of Life and Adaptation of Patients with Heart Failure to Their Disease in Shushtar, Khuzestan Province. Jundishapur Journal Of Chronic Disease Care. 2017 Jan 31;6(1). [10.17795/jjcdc-38460]
[7] Sung MM, Dyck JR. Therapeutic potential of resveratrol in heart failure. Annals of the New York Academy of Sciences. 2015 Aug;1348(1):32-45. [10.1111/nyas.12839 ] [PMID]
[8] Aimo A, Vergaro G, Passino C, Clerico A. Evaluation of pathophysiological relationships between renin-angiotensin and ACE-ACE2 systems in cardiovascular disorders: From theory to routine clinical practice in patients with heart failure. Critical Reviews in Clinical Laboratory Sciences. 2021 Nov 17;58(8):530-45. [10.1080/10408363. 2021.1942782] [PMID]
[9] Fischer C. A patent review of apelin receptor (APJR) modulators (2014-2019). Expert Opinion on Therapeutic Patents. 2020 Apr 2;30(4):251-61. [10.1080/13543776.2020.1731473 ] [PMID]
[10] Tatemoto K, Hosoya M, Habata Y, Fujii R, Kakegawa T, Zou MX, Kawamata Y, Fukusumi S, Hinuma S, Kitada C, Kurokawa T. Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor. Biochemical and biophysical research communications. 1998 Oct 20;251(2):471-6. [10.1006/bbrc.1998.9489 ] [PMID]
[11] Chandrasekaran B, Dar O, McDonagh T. The role of apelin in cardiovascular function and heart failure. European journal of heart failure. 2008 Aug;10(8):725-32. [10.1006/bbrc.1998.9489 ] [PMID]
[12] Jiang W, Hu W, Ye L, Tian Y, Zhao R, Du J, Shen B, Wang K. Contribution of Apelin-17 to collateral circulation following cerebral ischemic stroke. Translational Stroke Research. 2019 Jun 15;10:298-307.. [10.1007/ s12975-018-0638-7] [PMID].
[13] Cano Martinez LJ, Coral Vazquez RM, Méndez JP, Trejo S, Perez Razo JC, Canto P. Serum concentrations of apelin-17 isoform vary in accordance to blood pressure categories in individuals with obesity class 3. Clinical and Experimental Hypertension. 2019;41(2):168-73. [10.1080/1064 1963.2018.1462374] [PMID]
[14] Piepoli MF, Binno S, Coats AJ, Cohen‐Solal A, Corrà U, Davos CH, Jaarsma T, Lund L, Niederseer D, Orso F, Villani GQ. Regional differences in exercise training implementation in heart failure: findings from the Exercise Training in Heart Failure (ExTraHF) survey. European journal of heart failure. 2019 Sep;21(9):1142-8. [10.1002/ejhf.1538 ] [PMID]
[15] Tucker WJ, Beaudry RI, Liang Y, Clark AM, Tomczak CR, Nelson MD, Ellingsen O, Haykowsky MJ. Meta-analysis of exercise training on left
ventricular ejection fraction in heart failure with reduced ejection fraction: a 10-year update. Progress in cardiovascular diseases. 2019 Mar 1;62(2):163-71. [10.1016/j.pcad.2018.08.006 ] [PMID]
[16] Russell SD, Saval MA, Robbins JL, Ellestad MH, Gottlieb SS, Handberg EM, Zhou Y, Chandler B, HF-ACTION Investigators. New York Heart Association functional class predicts exercise parameters in the current era. American heart journal. 2009 Oct 1;158(4):S24-30. [10.1016/ j.ahj.2009.07.017 ] [PMID]
[17] Han C, Xian Z, Zou Y, Liao Z, Yang R, Zou C, Wang X, Sun Y. Flow-mediated dilation can be used to predict incident hypertension in patients with hyperuricemia. Archives of Medical Science. 2019 Mar 1;15(2):343-9. [10.5114/aoms.2018.73856 ] [PMID]
[18] Mahmoodinezhad S, Shakerian S, Ghalavand A, Motamedi P, Delaramnasab M. The Effect of acute training and circadian rhythm on blood hemostasis in female athletes. International Journal of Basic Science in Medicine. 2016 Jun 22;1(1):8-12. [10.15171/ijbsm.2016.03]
[19] Ghalavand A, Shakeriyan S, Monazamnezhad A, Delaramnasab M. The effect of resistance training on cardio-metabolic factors in males with type 2 diabetes. Jundishapur Journal of Chronic Disease Care. 2014 Oct 1;3(4). [10.17795/jjcdc-23346]
[20] Zucker IH, Schultz HD, Patel KP, Wang H. Modulation of angiotensin II signaling following exercise training in heart failure. American Journal of Physiology-Heart and Circulatory Physiology. 2015 Apr 15;308(8): H781-91. [10.1152/ajpheart.00026.2015 ] [PMID]
[21] Alenina N, dos Santos RA. Angiotensin-(1-7) and Mas: a brief history. The Protective Arm of the Renin Angiotensin System (RAS). 2015:155. [10.1016/B978-0-12-801364-9.00021-3]
[22] Magalhães DM, Nunes-Silva A, Rocha GC, Vaz LN, de Faria MH, Vieira EL, Rocha NP, e Silva AC. Two protocols of aerobic exercise modulate the counter-regulatory axis of the renin-angiotensin system. Heliyon. 2020 Jan 1;6(1). [10.1016/j.heliyon.2020.e03208] [PMID]
[23] Alexandre-Santos B, Giori IG, de Oliveira Medeiros GR, Vieira CP, Conte-Junior CA, da Nobrega AC, Frantz ED. Renin-angiotensin system modulation through enalapril and/or exercise training improves visceral adiposity in obese mice. Life Sciences. 2022 Feb 15;291:120269.
[10.1016/j.lfs.2021.120269] [PMID]
[24] Jokar M, Ghalavand A. Improving endothelial function following regular pyramid aerobic training in patients with type 2 diabetes. Razi Journal of Medical Sciences. 2021 Sep 10;28(6):60-9. [Link]
[25] Green DJ, Maiorana A, O'Driscoll G, Taylor R. Effect of exercise training on endothelium‐derived nitric oxide function in humans. The Journal of physiology. 2004 Nov;561(1):1-25 .[ 10.1113/jphysiol.2004.068197 ] [PMID]
[26] .Fernandez KX, Fischer C, Vu J, Gheblawi M, Wang W, Gottschalk S, Iturrioz X, Llorens-Cortés C, Oudit GY, Vederas JC. Metabolically stable apelin-analogues, incorporating cyclohexylalanine and homoarginine, as potent apelin receptor activators. RSC Medicinal Chemistry. 2021;12(8):1402-13. [10.1039/d1md00120e] [PMID]
[27] Fujie S, Sato K, Miyamoto-Mikami E, Hasegawa N, Fujita S, Sanada K, Hamaoka T, Iemitsu M. Reduction of arterial stiffness by exercise training is associated with increasing plasma apelin level in middle-aged and older adults. PloS one. 2014 Apr 1;9(4):e93545. [10.1039/ d1md00120e] [PMID]
[28] Son JS, Chae SA, Park BI, Du M, Song W. Plasma apelin levels in overweight/obese adults following a single bout of exhaustive exercise: A preliminary cross-sectional study. Endocrinologia, diabetes y nutricion. 2019 May 1;66(5):278-90 [10.1016/j.endinu.2018.12.005 ] [PMID]
[29] de Oliveira AA, Vergara A, Wang X, Vederas JC, Oudit GY. Apelin pathway in cardiovascular, kidney, and metabolic diseases: Therapeutic role of apelin analogs and apelin receptor agonists. Peptides. 2022 Jan 1;147:170697. [10.1016/j.peptides.2021.170697] [PMID]