The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
권호 표지
DOI QR코드

DOI QR Code

The effect of melatonin on cardio fibrosis in juvenile rats with pressure overload and deregulation of HDACs

  • Wu, Yao (Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders) ;
  • Si, Feifei (Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders) ;
  • Luo, Li (Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders) ;
  • Jing, Fengchuan (Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders) ;
  • Jiang, Kunfeng (Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders) ;
  • Zhou, Jiwei (Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders) ;
  • Yi, Qijian (Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders)
  • Received : 2017.06.26
  • Accepted : 2017.09.20
  • Published : 2018.11.01
Download PDF
⟨ Previous Next ⟩

Abstract

The effect of melatonin on juveniles with cardio fibrosis is poorly understood. We investigated whether HDACs participate in the anti-fibrotic processes regulated by melatonin during hypertrophic remodeling. Abdominal aortic constriction (AAC) was employed in juvenile rats resulting in pressure overload-induced ventricular hypertrophy and melatonin was subsequently decreased via continuous light exposure for 5 weeks after surgery. AAC rats displayed an increased cross-sectional area of myocardial fibers and significantly elevated collagen deposition compared to sham-operated rats, as measured by HE and Masson Trichrome staining. Continuous light exposure following surgery exacerbated the increase in the cross-sectional area of myocardial fibers. The expression of HDAC1, HDAC2, HDAC3, HDAC4 and HDAC6 genes were all significantly enhanced in AAC rats with light exposure relative to the other rats. Moreover, the protein level of $TNF-{\alpha}$ was also upregulated in the AAC light exposure groups when compared with the sham. However, Smad4 protein expression was unchanged in the juveniles' hearts. In contrast, beginning 5 weeks after the operation, the AAC rats were treated with melatonin (10 mg/kg, intraperitoneal injection every evening) or vehicle 4 weeks, and sham rats were given vehicle. The changes in the histological measures of cardio fibrosis and the gene expressions of HDAC1, HDAC2, HDAC3, HDAC4 and HDAC6 were attenuated by melatonin administration. The results reveal that melatonin plays a role in the development of cardio fibrosis and the expression of HDAC1, HDAC2, HDAC3, HDAC4 and HDAC6 in cardiomyocytes.

Keywords

References

  1. Reiter RJ, Melchiorri D, Sewerynek E, Poeggeler B, Barlow-Walden L, Chuang J, Ortiz GG, Acuna-Castroviejo D. A review of the evidence supporting melatonin's role as an antioxidant. J Pineal Res. 1995;18:1-11. https://doi.org/10.1111/j.1600-079X.1995.tb00133.x
  2. Tan DX, Reiter RJ, Manchester LC, Yan MT, El-Sawi M, Sainz RM, Mayo JC, Kohen R, Allegra M, Hardeland R. Chemical and physical properties and potential mechanisms: melatonin as a broad spectrum antioxidant and free radical scavenger. Curr Top Med Chem. 2002;2:181-197. https://doi.org/10.2174/1568026023394443
  3. Simko F, Pechanova O, Pelouch V, Krajcirovicova K, Celec P, Palffy R, Bednarova K, Vrankova S, Adamcova M, Paulis L. Continuous light and L-NAME-induced left ventricular remodelling: different protection with melatonin and captopril. J Hypertens. 2010;28 Suppl 1:S13-18. https://doi.org/10.1097/01.hjh.0000388489.28213.08
  4. Grossman E, Laudon M, Yalcin R, Zengil H, Peleg E, Sharabi Y, Kamari Y, Shen-Orr Z, Zisapel N. Melatonin reduces night blood pressure in patients with nocturnal hypertension. Am J Med. 2006;119:898-902. https://doi.org/10.1016/j.amjmed.2006.02.002
  5. Ferguson BS, McKinsey TA. Non-sirtuin histone deacetylases in the control of cardiac aging. J Mol Cell Cardiol. 2015;83:14-20. https://doi.org/10.1016/j.yjmcc.2015.03.010
  6. Schuetze KB, McKinsey TA, Long CS. Targeting cardiac fibroblasts to treat fibrosis of the heart: focus on HDACs. J Mol Cell Cardiol. 2014;70:100-107. https://doi.org/10.1016/j.yjmcc.2014.02.015
  7. Gallo P, Latronico MV, Gallo P, Grimaldi S, Borgia F, Todaro M, Jones P, Gallinari P, De Francesco R, Ciliberto G, Steinkuhler C, Esposito G, Condorelli G. Inhibition of class I histone deacetylase with an apicidin derivative prevents cardiac hypertrophy and failure. Cardiovasc Res. 2008;80:416-424. https://doi.org/10.1093/cvr/cvn215
  8. Kang SH, Seok YM, Song MJ, Lee HA, Kurz T, Kim I. Histone deacetylase inhibition attenuates cardiac hypertrophy and fibrosis through acetylation of mineralocorticoid receptor in spontaneously hypertensive rats. Mol Pharmacol. 2015;87:782-791. https://doi.org/10.1124/mol.114.096974
  9. Wu TH, Kuo HC, Lin IC, Chien SJ, Huang LT, Tain YL. Melatonin prevents neonatal dexamethasone induced programmed hypertension: histone deacetylase inhibition. J Steroid Biochem Mol Biol. 2014;144:253-259. https://doi.org/10.1016/j.jsbmb.2014.07.008
  10. Hwang B, Qu TY, Hu CT, Chen HI. Hemodynamic and neurohumoral changes after abdominal aortic constriction in rats. Proc Natl Sci Counc Repub China B. 1999;23:149-157.
  11. Sehirli AO, Koyun D, Tetik S, Ozsavci D, Yiginer O, Cetinel S, Tok OE, Kaya Z, Akkiprik M, Kilic E, Sener G. Melatonin protects against ischemic heart failure in rats. J Pineal Res. 2013;55:138-148. https://doi.org/10.1111/jpi.12054
  12. Zhang S, Li H, Yang SJ. Tribulosin protects rat hearts from ischemia/reperfusion injury. Acta Pharmacol Sin. 2010;31:671-678. https://doi.org/10.1038/aps.2010.45
  13. Kang S, Liu Y, Sun D, Zhou C, Liu A, Xu C, Hao Y, Li D, Yan C, Sun H. Chronic activation of the G protein-coupled receptor 30 with agonist G-1 attenuates heart failure. PLoS One. 2012;7:e48185. https://doi.org/10.1371/journal.pone.0048185
  14. Williams SM, Golden-Mason L, Ferguson BS, Schuetze KB, Cavasin MA, Demos-Davies K, Yeager ME, Stenmark KR, McKinsey TA. Class I HDACs regulate angiotensin II-dependent cardiac fibrosis via fibroblasts and circulating fibrocytes. J Mol Cell Cardiol. 2014;67:112-125. https://doi.org/10.1016/j.yjmcc.2013.12.013
  15. Mizrak B, Parlakpinar H, Acet A, Turkoz Y. Effects of pinealectomy and exogenous melatonin on rat hearts. Acta Histochem. 2004;106:29-36. https://doi.org/10.1016/j.acthis.2003.10.003
  16. Lee E, Song MJ, Lee HA, Kang SH, Kim M, Yang EK, Lee do Y, Ro S, Cho JM, Kim I. Histone deacetylase inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats. Korean J Physiol Pharmacol. 2016;20:477-485. https://doi.org/10.4196/kjpp.2016.20.5.477
  17. Lochner A, Huisamen B, Nduhirabandi F. Cardioprotective effect of melatonin against ischaemia/reperfusion damage. Front Biosci (Elite Ed). 2013;5:305-315.
  18. Lkhagva B, Lin YK, Kao YH, Chazo TF, Chung CC, Chen SA, Chen YJ. Novel histone deacetylase inhibitor modulates cardiac peroxisome proliferator-activated receptors and inflammatory cytokines in heart failure. Pharmacology. 2015;96:184-191. https://doi.org/10.1159/000438864
  19. Hohl M, Wagner M, Reil JC, Muller SA, Tauchnitz M, Zimmer AM, Lehmann LH, Thiel G, Bohm M, Backs J, Maack C. HDAC4 controls histone methylation in response to elevated cardiac load. J Clin Invest. 2013;123:1359-1370. https://doi.org/10.1172/JCI61084
  20. Sucharov CC, Dockstader K, McKinsey TA. YY1 protects cardiac myocytes from pathologic hypertrophy by interacting with HDAC5. Mol Biol Cell. 2008;19:4141-4153. https://doi.org/10.1091/mbc.e07-12-1217
  21. Trivedi CM, Luo Y, Yin Z, Zhang M, Zhu W, Wang T, Floss T, Goettlicher M, Noppinger PR, Wurst W, Ferrari VA, Abrams CS, Gruber PJ, Epstein JA. Hdac2 regulates the cardiac hypertrophic response by modulating Gsk3 beta activity. Nat Med. 2007;13:324-331. https://doi.org/10.1038/nm1552
  22. Korkmaz A, Rosales-Corral S, Reiter RJ. Gene regulation by melatonin linked to epigenetic phenomena. Gene. 2012;503:1-11. https://doi.org/10.1016/j.gene.2012.04.040
  23. Bradham WS, Bozkurt B, Gunasinghe H, Mann D, Spinale FG. Tumor necrosis factor-alpha and myocardial remodeling in progression of heart failure: a current perspective. Cardiovasc Res. 2002;53:822-830. https://doi.org/10.1016/S0008-6363(01)00503-X
  24. Gupta S, Tripathi CD. Current status of TNF blocking therapy in heart failure. Indian J Med Sci. 2005;59:363-366. https://doi.org/10.4103/0019-5359.16655
  25. Shaki F, Ashari S, Ahangar N. Melatonin can attenuate ciprofloxacin induced nephrotoxicity: Involvement of nitric oxide and $TNF-{\alpha}$. Biomed Pharmacother. 2016;84:1172-1178. https://doi.org/10.1016/j.biopha.2016.10.053
  26. Hao J, Ju H, Zhao S, Junaid A, Scammell-La Fleur T, Dixon IM. Elevation of expression of Smads 2, 3, and 4, decorin and TGF-beta in the chronic phase of myocardial infarct scar healing. J Mol Cell Cardiol. 1999;31:667-678. https://doi.org/10.1006/jmcc.1998.0902
  27. Tsai JW, Hannibal J, Hagiwara G, Colas D, Ruppert E, Ruby NF, Heller HC, Franken P, Bourgin P. Melanopsin as a sleep modulator: circadian gating of the direct effects of light on sleep and altered sleep homeostasis in Opn4(-/-) mice. PLoS Biol. 2009;7:e1000125. https://doi.org/10.1371/journal.pbio.1000125

Cited by

  1. Histone deacetylase 9 downregulation decreases tumor growth and promotes apoptosis in non‐small cell lung cancer after melatonin treatment vol.67, pp.2, 2018, https://doi.org/10.1111/jpi.12587
  2. A Peptide-Functionalized Magnetic Nanoplatform-Loaded Melatonin for Targeted Amelioration of Fibrosis in Pressure Overload-Induced Cardiac Hypertrophy vol.15, pp.None, 2018, https://doi.org/10.2147/ijn.s235518
  3. NICEdrug.ch, a workflow for rational drug design and systems-level analysis of drug metabolism vol.10, pp.None, 2018, https://doi.org/10.7554/elife.65543
  4. Nutraceutical, Dietary, and Lifestyle Options for Prevention and Treatment of Ventricular Hypertrophy and Heart Failure vol.22, pp.7, 2021, https://doi.org/10.3390/ijms22073321
  5. Histone deacetylase HDAC4 participates in the pathological process of myocardial ischemia-reperfusion injury via MEKK1/JNK pathway by binding to miR-206 vol.7, pp.1, 2018, https://doi.org/10.1038/s41420-021-00601-1
  6. The miR‐455‐3p/HDAC2 axis plays a pivotal role in the progression and reversal of liver fibrosis and is regulated by epigenetics vol.35, pp.7, 2018, https://doi.org/10.1096/fj.202002319rrr