The Korean Journal of Physiology and Pharmacology

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

DOI QR Code

Exploring the beneficial role of telmisartan in sepsis-induced myocardial injury through inhibition of high-mobility group box 1 and glycogen synthase kinase-3β/nuclear factor-κB pathway

  • Jin, Yan (Emergency Department, Second Affiliated Hospital of Dalian Medical University Dalian) ;
  • Wang, Hong (Emergency Department, Second Affiliated Hospital of Dalian Medical University Dalian) ;
  • Li, Jing (Department of Cardiology, Hospital Affiliated to Shenyang Medical College) ;
  • Dang, Minyan (Innoscience Research Sdn Bhd) ;
  • Zhang, Wenzhi (Innoscience Research Sdn Bhd) ;
  • Lei, Yan (Innoscience Research Sdn Bhd) ;
  • Zhao, Hao (Emergency Department, Affiliated Hospital of Shandong University of Traditional Chinese Medicine)
  • Received : 2020.01.09
  • Accepted : 2020.01.31
  • Published : 2020.07.01
Download PDF
⟨ Previous Next ⟩

Abstract

In the present experimental study, cecal ligation and puncture significantly increased the myocardial injury assessed in terms of excess release of creative kinase-MB (CK-MB), cardiac troponin I (cTnI), interleukin (IL)-6 and decrease of IL-10 in the blood following 12 h of laparotomy procedure as compared to normal control. Also, a significant increase in protein expression levels of high-mobility group box 1 (HMGB1) and decreased phosphorylation of glycogen synthase kinase-3β (GSK-3β) was observed in the myocardial tissue as compared to normal control. A single independent administration of telmisartan (2 and 4 mg/kg) and AR-A014418 (1 and 2 mg/kg) substantially reduced sepsis-induced myocardial injury in terms of decrease levels of CK-MB, cTnI and IL-6, HMGB1, GSK-3β and increase in IL-10 and p-GSK-3β in the blood in sepsis- subjected rats. The effects of telmisartan at dose 4 mg/kg and AR-A014418 at a dose of 2 mg/kg were significantly higher than the telmisartan at a dose of 2 mg/kg and AR-A014418 1 mg/kg respectively. Further, no significant effects on different parameters were observed in the sham control group in comparison to normal. Therefore it is plausible to suggest that sepsis may increase the levels of angiotensin II to trigger GSK-3β-dependent signaling to activate the HMGB1/receptors for advanced glycation end products, which may promote inflammation and myocardial injury in sepsis-subjected rats.

Keywords

References

  1. Sagy M, Al-Qaqaa Y, Kim P. Definitions and pathophysiology of sepsis. Curr Probl Pediatr Adolesc Health Care. 2013;43:260-263. https://doi.org/10.1016/j.cppeds.2013.10.001
  2. Walley KR. Sepsis-induced myocardial dysfunction. Curr Opin Crit Care. 2018;24:292-299. https://doi.org/10.1097/MCC.0000000000000507
  3. Wang Z, Bu L, Yang P, Feng S, Xu F. Alleviation of sepsis-induced cardiac dysfunction by overexpression of Sestrin2 is associated with inhibition of p-S6K and activation of the p-AMPK pathway. Mol Med Rep. 2019;20:2511-2518.
  4. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29:1303-1310. https://doi.org/10.1097/00003246-200107000-00002
  5. Sifi A, Adi-Bessalem S, Laraba-Djebari F. Role of angiotensin II and angiotensin type-1 receptor in scorpion venom-induced cardiac and aortic tissue inflammation. Exp Mol Pathol. 2017;102:32-40. https://doi.org/10.1016/j.yexmp.2016.11.006
  6. Wang H, Ward MF, Sama AE. Novel HMGB1-inhibiting therapeutic agents for experimental sepsis. Shock. 2009;32:348-357. https://doi.org/10.1097/SHK.0b013e3181a551bd
  7. Tieu BC, Lee C, Sun H, Lejeune W, Recinos A 3rd, Ju X, Spratt H, Guo DC, Milewicz D, Tilton RG, Brasier AR. An adventitial IL-6/ MCP1 amplification loop accelerates macrophage-mediated vascular inflammation leading to aortic dissection in mice. J Clin Invest. 2009;119:3637-3651. https://doi.org/10.1172/JCI38308
  8. Xu J, Carretero OA, Liao TD, Peng H, Shesely EG, Xu J, Liu TS, Yang JJ, Reudelhuber TL, Yang XP. Local angiotensin II aggravates cardiac remodeling in hypertension. Am J Physiol Heart Circ Physiol. 2010;299:H1328-H1338. https://doi.org/10.1152/ajpheart.00538.2010
  9. Tsung A, Sahai R, Tanaka H, Nakao A, Fink MP, Lotze MT, Yang H, Li J, Tracey KJ, Geller DA, Billiar TR. The nuclear factor HMGB1 mediates hepatic injury after murine liver ischemia-reperfusion. J Exp Med. 2005;201:1135-1143. https://doi.org/10.1084/jem.20042614
  10. Bangert A, Andrassy M, Muller AM, Bockstahler M, Fischer A, Volz CH, Leib C, Goser S, Korkmaz-Icoz S, Zittrich S, Jungmann A, Lasitschka F, Pfitzer G, Muller OJ, Katus HA, Kaya Z. Critical role of RAGE and HMGB1 in inflammatory heart disease. Proc Natl Acad Sci U S A. 2016;113:E155-E164. https://doi.org/10.1073/pnas.1522288113
  11. Volz HC, Kaya Z, Katus HA, Andrassy M. The role of HMGB1/RAGE in inflammatory cardiomyopathy. Semin Thromb Hemost. 2010;36:185-194. https://doi.org/10.1055/s-0030-1251503
  12. Wen H. Sepsis induced by cecal ligation and puncture. Methods Mol Biol. 2013;1031:117-124. https://doi.org/10.1007/978-1-62703-481-4_15
  13. Faix JD. Biomarkers of sepsis. Crit Rev Clin Lab Sci. 2013;50:23-36. https://doi.org/10.3109/10408363.2013.764490
  14. Takahashi-Yanaga F. Roles of glycogen synthase kinase-3 (GSK-3) in cardiac development and heart disease. J UOEH. 2018;40:147-156. https://doi.org/10.7888/juoeh.40.147
  15. Wei D, Xu H, Gai X, Jiang Y. Astragaloside IV alleviates myocardial ischemia-reperfusion injury in rats through regulating PI3K/AKT/ GSK-$3{\beta}$ signaling pathways. Acta Cir Bras. 2019;34:e201900708. https://doi.org/10.1590/s0102-865020190070000008
  16. Wong R, Aponte AM, Steenbergen C, Murphy E. Cardioprotection leads to novel changes in the mitochondrial proteome. Am J Physiol Heart Circ Physiol. 2010;298:H75-H91. https://doi.org/10.1152/ajpheart.00515.2009
  17. Wichterman KA, Baue AE, Chaudry IH. Sepsis and septic shock--a review of laboratory models and a proposal. J Surg Res. 1980;29:189-201. https://doi.org/10.1016/0022-4804(80)90037-2
  18. Kikuchi K, Tancharoen S, Ito T, Morimoto-Yamashita Y, Miura N, Kawahara K, Maruyama I, Murai Y, Tanaka E. Potential of the angiotensin receptor blockers (ARBs) telmisartan, irbesartan, and candesartan for inhibiting the HMGB1/RAGE axis in prevention and acute treatment of stroke. Int J Mol Sci. 2013;14:18899-18924. https://doi.org/10.3390/ijms140918899
  19. Nakamura K, Yamagishi S, Nakamura Y, Takenaka K, Matsui T, Jinnouchi Y, Imaizumi T. Telmisartan inhibits expression of a receptor for advanced glycation end products (RAGE) in angiotensin- II-exposed endothelial cells and decreases serum levels of soluble RAGE in patients with essential hypertension. Microvasc Res. 2005;70:137-141. https://doi.org/10.1016/j.mvr.2005.10.002
  20. Zhang S, Qi W, Wang F, Xu Y, Wang X. [Effects of carbon monoxide release molecule-2 on sepsis-induced myocardial dysfunction in rats]. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2019;31:1097-1101. Chinese.
  21. Lu ZQ, Lu JX, Deng YJ. Glucocorticoids offer protection against myocardial injury in a murine model of sepsis. Int J Clin Exp Med. 2015;8:12211-12218.
  22. Sharma HS, Das DK. Role of cytokines in myocardial ischemia and reperfusion. Mediators Inflamm. 1997;6:175-183. https://doi.org/10.1080/09629359791668
  23. Li X, Cheng Q, Li J, He Y, Tian P, Xu C. Significance of hydrogen sulfide in sepsis-induced myocardial injury in rats. Exp Ther Med. 2017;14:2153-2161. https://doi.org/10.3892/etm.2017.4742
  24. O'Riordan CE, Purvis GSD, Collotta D, Chiazza F, Wissuwa B, Al Zoubi S, Stiehler L, Martin L, Coldewey SM, Collino M, Thiemermann C. Bruton's tyrosine kinase inhibition attenuates the cardiac dysfunction caused by cecal ligation and puncture in mice. Front Immunol. 2019;10:2129. https://doi.org/10.3389/fimmu.2019.02129
  25. Wang H, Bloom O, Zhang M, Vishnubhakat JM, Ombrellino M, Che J, Frazier A, Yang H, Ivanova S, Borovikova L, Manogue KR, Faist E, Abraham E, Andersson J, Andersson U, Molina PE, Abumrad NN, Sama A, Tracey KJ. HMG-1 as a late mediator of endotoxin lethality in mice. Science. 1999;285:248-251. https://doi.org/10.1126/science.285.5425.248
  26. Zhen J, Li L, Yan J. [Advances in biomarkers of myocardial injury in sepsis]. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2018;30:699-702. Chinese.
  27. Xin Y, Bai Y, Jiang X, Zhou S, Wang Y, Wintergerst KA, Cui T, Ji H, Tan Y, Cai L. Sulforaphane prevents angiotensin II-induced cardiomyopathy by activation of Nrf2 via stimulating the Akt/GSK-3b/Fyn pathway. Redox Biol. 2018;15:405-417. https://doi.org/10.1016/j.redox.2017.12.016

Cited by

  1. Involvement of BDNF Signalling Pathway in Spironolactone- Mediated Protective Effects in Sepsis-Induced Cardiac Injury in Rats vol.17, pp.8, 2020, https://doi.org/10.3923/ijp.2021.577.583