Expression of apelin is related to oxidative damage in heart tissue of rats during chronic systemic hypoxia

  • H R Helmi Department of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Tarumanagara, Jakarta
  • Frans Ferdinal Department of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Tarumanagara, Jakarta
  • Ani Retno Prijanti Department of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Indonesia, Jakarta
  • Sri Widia A Jusman Department of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Indonesia, Jakarta https://orcid.org/0000-0003-0471-5583
  • Frans D Suyatna Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta
Keywords: Apelin, Malondialdehyde, Chronic systemic hypoxia, Cardiac hypertrophy

Abstract

Background: Chronic systemic hypoxia is severe environmental stress for the heart and might lead to the development of heart failure. Apelin is an endogenous peptide that has been shown to have various beneficial effects on cardiac function. Apelin appears to have a role to play in the ventricular dysfunction and maintaining the performance of the heart.

Objectives: In the present study we want to investigate the adaptive response of heart tissue to chronic systemic hypoxia and the correlation with apelin expression and oxidative stress in rat. 

Methods: An experimental study was performed using 28 Sprague-Dawley male rats, 8 weeks of age. Rats were divided into 7 groups 4 each, namely control group; normoxia (O2 atmosphere) and the treatment group of hypoxia (8% O2) for 6 hours; 1;3;5;7 and 14 days respectively. Body weight and heart weight were measured at each treatment. Ventricular thickness was measured by caliper, Apelin mRNA was measured using real-time qRT-PCR with Livak formula and malondialdehyde (MDA) level was used to assess oxidative stress due to cardiac tissue hypoxia.

Results: Macroscopic exams showed hypertrophy at day 7th. The relative expression of Apelin mRNA in hypoxic heart is decreased at the beginning and then increased, starting from day-7 to day-14. The MDA levels were significantly increased from day-7 and were strongly correlated with relative expression Apelin.

Conclusion:  It is concluded that the increase of Apelin expression is related to oxidative stress in heart tissue of rats during chronic systemic hypoxia.

References

Corno AF, Milano G, Samaja M, Tozzi P, von Segesser LK. Chronic hypoxia: A model for cyanotic congenital heart defects, J. Thorac Cardiovasc. Surg. 2002;124(1):105-12. https://doi.org/10.1067/mtc.2002.121302

Giordano FJ. Oxygen, oxidative stress, hypoxia, and heart failure. J Clin Invest. 2005;115(3):500-8. https://doi.org/10.1172/JCI200524408

Bupha-Intr T, Holmes JW, Janssen PM. Induction of hypertrophy in vitro by mechanical loading in adult rabbit myocardium. Am J Physiol Heart Circ Physiol. 2007; H3759-H3767. https://doi.org/10.1152/ajpheart.01267.2006

Schultz Jel J, Witt SA, Glascock BJ, Nieman ML, Reiser PJ, Nixet SL, et al. TGF-beta1 mediates the hypertrophic cardiomyocyte growth induced by angiotensin II. J Clin Invest. 2002;109(6):787-96. https://doi.org/10.1172/JCI0214190

Houser SR, Margulies KB, Murphy AM, Spinale FG, Francis GS, Prabhu SD, et al. Animal Models of Heart Failure. Circ Res. 2012;111:131-150. https://doi.org/10.1161/RES.0b013e3182582523

Lorell BH, Carabello BA. Left ventricular hypertrophy: pathogenesis, detection and prognosis. Circulation. 2000;102:470-479. https://doi.org/10.1161/01.CIR.102.4.470

Lindenfeld J, Albert NM, Boehmer JP, Collins SP, Ezekowitz JA, Givertz MM, et al. HFSA 2010 Comprehensive heart failure practice guideline. J Card Fail. 2010;16(6):e1-194. https://doi.org/10.1016/j.cardfail.2010.04.004

Mulders F, Elsner D. Animal models of chronic heart failure. Pharmacol Res. 2000;41(6):605-612. https://doi.org/10.1006/phrs.1999.0652

Wu S, Gao J, Ohlemeyer C, Roos D, Niessen H, Köttgen E, et al. Activation of AP-1 through reactive oxygen species by angiotensin II in rat cardiomyocytes. Free Radic Biol Med. 2005;39(12):1601-10. https://doi.org/10.1016/j.freeradbiomed.2005.08.006

Higuchi Y, Otsu K, Nishida K, Hirotani S, Nakayama H, Yamaguchi O, et al. Involvement of reactive oxygen species-mediated NF-kappa B activation in TNF-alpha-induced cardiomyocyte hypertrophy. J Mol Cell Cardiol. 2002;34(2):233-40. https://doi.org/10.1006/jmcc.2001.1505

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. https://doi.org/10.1016/j.febslet.2010.04.025

Hori M, Nishida K. Oxidative stress and left ventricular remodelling after myocardial infarction. Cardiovasc Res. 2009;81:457-64. https://doi.org/10.1093/cvr/cvn335

Nakagami H, Takemoto M, Liao JK. NADPH oxidase-derived superoxide anion mediates angiotensin II-induced cardiac hypertrophy.J Mol Cell Cardiol. 2003;35(7):851-9. https://doi.org/10.1016/S0022-2828(03)00145-7

Wills ED. Evaluation of lipid peroxidation in lipids and biological membranes. In: Snell K, Mullock B, editors. Biochemical toxicology: a practical approach. Oxford: IRL, 1987.

Tatemoto K, Takayama K, Zou MX, Kumaki I, Zhang W, Kumano K, et al. The novel peptide apelin lowers blood pressure via a nitric oxide-dependent mechanism. Regul. Pept. 2001:99, 87-92. https://doi.org/10.1016/S0167-0115(01)00236-1

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;65:73-82. https://doi.org/10.1016/j.cardiores.2004.08.018

Chandrasekaran B, Dar O, McDonagh T. The role of apelin in cardiovascular function and heart failure. Eur J Heart Fail. 2008;10:725-32. https://doi.org/10.1016/j.ejheart.2008.06.002

Masri BB, Knibiehler, Audigier Y. Apelin signalling: a promising pathway from cloning to pharmacology. Cell. Signal. 2005;17,415-426. https://doi.org/10.1016/j.cellsig.2004.09.018

Japp AG, Newby DE. The apelin-APJ system in heart failure: pathophysiologic relevance and therapeutic potential. Biochem Pharmacol. 2008;75(10):1882-92. https://doi.org/10.1016/j.bcp.2007.12.015

O'Carroll AM, Lolait SJ, Harris LE, Pope GR. The apelin receptor APJ: journey from an orphan to a multifaceted regulator of homeostasis. J. Endocrinol. 2013;219,R13-R35. https://doi.org/10.1530/JOE-13-0227

Sheikh AY, Chun HJ, Glassford AJ, Kundu RK, Kutschka I, Ardigo D, et al. In vivo genetic profiling and cellular localization of apelin reveals a hypoxia-sensitive, endothelial-centered pathway activated in ischemic heart failure. Am J Physiol Heart Circ Physiol. 2008;294:H88-98. https://doi.org/10.1152/ajpheart.00935.2007

Japp AG, Cruden NL, Amer DA, Li VK, Goudie EB, Johnston NR, et al. Vascular effects of apelin in vivo in man. J Am Coll Cardiol. 2008;52:908-13. https://doi.org/10.1016/j.jacc.2008.06.013

Kunduzova O, Alet N, Delesque-Touchard N, Millet L, Castan-Laurell I, Muller C, et al. Apelin/APJ signaling system: a potential link between adipose tissue and endothelial angiogenic processes. FASEB J. 2008;22:4146-53. https://doi.org/10.1096/fj.07-104018

Szokodi I, Tavi P, Foldes G, Voutilainen-Myllyla S, Ilves M, Tokola H, et al. Apelin, the novel endogenous ligand of the orphan receptor APJ, regulates cardiac contractility. Circ Res. 2002;91:434-40. https://doi.org/10.1161/01.RES.0000033522.37861.69

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. https://doi.org/10.1016/j.bbrc.2007.04.017

Chapman NA, Dupre DJ, Rainey JK. The apelin receptor: physiology, pathology, cell signalling, and ligand modulation of a peptide-activated class A GPCR. Biochem.Cell.Biol. 2014:92,431-440. https://doi.org/10.1139/bcb-2014-0072

Zhong JC, Yu XY, Huang Y, Yung LM, Lau CW, Lin SG. Apelin modulates aortic vascular tone via endothelial nitric oxide synthase phosphorylation pathway in diabetic mice. Cardiovasc Res. 2007;74:388-95. https://doi.org/10.1016/j.cardiores.2007.02.002

Koguchi W, Kobayashi N, Takeshima H, Ishikawa M, Sugiyama F, Ishimitsu T. Cardioprotective effect of apelin-13 on cardiac performance and remodeling in end-stage heart failure. Circ J. 2012;76:137-44. https://doi.org/10.1253/circj.CJ-11-0689

Ronkainen VP, Ronkainen JJ, Hanninen SL, Leskinen H, Ruas JL, Pereira T, et al. Hypoxia inducible factor regulates the cardiac expression and secretion of apelin. FASEB J. 2007;21:1821-30. https://doi.org/10.1096/fj.06-7294com

Ferdinal F, Suyatna FD, Wanandi SI, Sadikin M. Expression of B-type natriuretic peptide-45 gene in the ventricular myocardial induced by systemic chronic hypoxia. Acta Med Indones. 2009;41(3): 136-43.

Witt KA, Mark KS, Hom S, Davis TP. Effects of hypoxia - reoxygenation on rat blood - brain barrier permeability and tight junctional protein expression. Am J Physiol Heart Circ Physiol. 2003;285:H2820-H2831 https://doi.org/10.1152/ajpheart.00589.2003

Ferdinal F, Suyatna FD, Wanandi SI, Sadikin M. Structural and morphological changes in rat ventricular myocardium induced by chronic systemic hypoxia. Acta Med Indones. 2010; 42(3): 135-41.

Xu X, Zhao W, Lao S, Wilson BS, Erikson JM, Zhang JQ. Effects of exercise and L-arginine on ventricular remodeling and oxidative stress. Med Sci Sports Exerc. 2010;42:346-54. https://doi.org/10.1249/MSS.0b013e3181b2e899

Movafagh S, Crook S, Vo K. Regulation of hypoxia-inducible factor-1α by reactive oxygen species: new developments in an old debate. J Cell Biochem. 2015;116(5):696-703. https://doi.org/10.1002/jcb.25074

oldes G, Horkay F, Szokodi I, Vuolteenaho O, Ilves M, Lindstedt KA, et al. Circulating and cardiac levels of apelin, the novel ligand of the orphan receptor APJ, in patients with heart failure. Biochem Biophys Res Commun. 2003;308, 480-485. https://doi.org/10.1016/S0006-291X(03)01424-4

Chen MM, Ashley EA, Deng DXF, Tsalenko A, Deng A, Tabibiazar R, et al. Novel role for the potent endogenous inotrope apelin in human cardiac dysfunction. Circulation. 2003;108, 1432-1439. https://doi.org/10.1161/01.CIR.0000091235.94914.75

Folden DV, Gupta A, Sharma AC, Li SY, Saari JT, Ren J. Malondialdehyde inhibits cardiac contractile function in ventricular myocytes via a p38 mitogen-activated protein kinase-dependent mechanism. Br J Pharmacol. 2003;139(7):1310-6. https://doi.org/10.1038/sj.bjp.0705384

Lee R, Margaritis M, Channon KM, Antoniades C. Evaluating oxidative stress in human cardiovascular disease: methodological aspects and considerations. Curr Med Chem. 2012;19(16):2504-20. https://doi.org/10.2174/092986712800493057

Noeman SA, Hamooda HE, Baalash AA. Biochemical study of oxidative stress markers in the liver, kidney and heart of high fat diet induced obesity in rats. Diabetol Metab Syndr. 2011;3(1):17. https://doi.org/10.1186/1758-5996-3-17

Published
2018-12-31
How to Cite
Helmi, H. R., Ferdinal, F., Prijanti, A. R., Jusman, S. W. A., & Suyatna, F. D. (2018). Expression of apelin is related to oxidative damage in heart tissue of rats during chronic systemic hypoxia. Acta Biochimica Indonesiana, 1(2), 68-78. https://doi.org/10.32889/actabioina.v1i2.18