Protective effects of GV1001 on myocardial ischemia‑reperfusion injury

Chang,Ji‑Eun; Kim,Hyun Jun; Jheon,Sanghoon; Lim,Cheong

doi:10.3892/mmr.2017.7528

Protective effects of GV1001 on myocardial ischemia‑reperfusion injury

Authors:
- Ji‑Eun Chang
- Hyun Jun Kim
- Sanghoon Jheon
- Cheong Lim
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Affiliations: Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital, Seongnam‑si, Gyeonggi‑do 13620, Republic of Korea
Published online on: September 19, 2017 https://doi.org/10.3892/mmr.2017.7528
Pages: 7315-7320
Copyright: © Chang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The potential cardioprotective effects of the novel vaccine peptide GV1001 were evaluated in myocardial ischemia‑reperfusion injury induced rat models. GV1001 is a human telomerase reverse transcriptase derived peptide, which has been reported to possess both anti‑tumor and anti‑inflammatory effects. The normal saline (control group) and various concentrations (0.001‑10 mg/kg) of GV1001 were administered directly to the right ventricle anterior wall before induction of ischemia. The was induced by Tightening the snare around the left anterior descending coronary artery for 40 min, before releasing the snare for 10 min induced the myocardial ischemia‑reperfusion injury and was conducted in Sprague‑Dawley rats. The area at risk, histology, apoptotic cells, neutrophils and inflammatory cytokines were analyzed from the excised heart tissue following myocardial ischemia‑reperfusion injury. The area at risk was protected by concentrations of GV1001 equal to or higher than 0.01 mg/kg. At 0.1 mg/kg and higher concentrations of GV1001, the hemorrhage in the heart was attenuated, while severe congestion was reported in the control group. Apoptotic cells, myeloperoxidase activity and inflammatory cytokines [tumor necrosis factor (TNF)‑α and interleukin (IL)‑6] revealed decreased levels in a dose‑dependent manner with respect to GV1001 concentration. The group treated with 10 mg/kg GV1001 demonstrated 59.73% apoptotic cells (P<0.001), 48.14% neutrophil contents (P<0.001), 55.63% TNF‑α (P<0.01) and 42.35% IL‑6 (P<0.01) levels, compared with the control group. The novel vaccine peptide GV1001 provided protective effects on myocardial ischemia‑reperfusion injury and, therefore, it should be considered as an alternative potential anti‑inflammatory agent for myocardial ischemia‑reperfusion injury.

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1	Boyle EM, Pohlman TH, Cornejo CJ and Verrier ED: Ischemia-reperfusion injury. Ann Thorac Surg. 64 Suppl:S24–S30. 1997. View Article : Google Scholar
2	Buja LM: Myocardial ischemia and reperfusion injury. Cardiovasc Pathol. 14:170–175. 2005. View Article : Google Scholar : PubMed/NCBI
3	Jordan JE, Zhao ZQ and Vinten-Johansen J: The role of neutrophils in myocardial ischemia-reperfusion injury. Cardiovasc Res. 43:860–878. 1999. View Article : Google Scholar : PubMed/NCBI
4	Liu Q, Li J, Jubair S, Wang D, Luo Y, Fan D and Janicki JS: Sparstolonin B attenuates hypoxia-induced apoptosis, necrosis and inflammation in cultured rat left ventricular tissue slices. Cardiovasc Drugs Ther. 28:433–439. 2014. View Article : Google Scholar : PubMed/NCBI
5	Hale SL and Kloner RA: Mild hypothermia as a cardioprotective approach for acute myocardial infarction: Laboratory to clinical application. J Cardiovasc Pharmacol Ther. 16:131–139. 2011. View Article : Google Scholar : PubMed/NCBI
6	Inderberg-Suso EM, Trachsel S, Lislerud K, Rasmussen AM and Gaudernack G: Widespread CD4⁺ T-cell reactivity to novel hTERT epitopes following vaccination of cancer patients with a single hTERT peptide GV1001. Oncoimmunology. 1:670–686. 2012. View Article : Google Scholar : PubMed/NCBI
7	Stevenson CL: Advances in peptide pharmaceuticals. Curr Pharm Biotechnol. 10:122–137. 2009. View Article : Google Scholar : PubMed/NCBI
8	Bernhardt SL, Gjertsen MK, Trachsel S, Møller M, Eriksen JA, Meo M, Buanes T and Gaudernack G: Telomerase peptide vaccination of patients with non-resectable pancreatic cancer: A dose escalating phase I/II study. Br J Cancer. 95:1474–1482. 2006. View Article : Google Scholar : PubMed/NCBI
9	Brunsvig PF, Aamdal S, Gjertsen MK, Kvalheim G, Markowski-Grimsrud CJ, Sve I, Dyrhaug M, Trachsel S, Møller M, Eriksen JA and Gaudernack G: Telomerase peptide vaccination: A phase I/II study in patients with non-small cell lung cancer. Cancer Immunol Immunother. 55:1553–1564. 2006. View Article : Google Scholar : PubMed/NCBI
10	Brunsvig PF, Kyte JA, Kersten C, Sundstrøm S, Møller M, Nyakas M, Hansen GL, Gaudernack G and Aamdal S: Telomerase peptide vaccination in NSCLC: A phase II trial in stage III patients vaccinated after chemoradiotherapy and an 8-year update on a phase I/II trial. Clin Cancer Res. 17:6847–6857. 2011. View Article : Google Scholar : PubMed/NCBI
11	Middleton G, Ghaneh P, Costello E, Greenhalf W and Neoptolemos JP: New treatment options for advanced pancreatic cancer. Expert Rev Gastroenterol Hepatol. 2:673–696. 2008. View Article : Google Scholar : PubMed/NCBI
12	Greten TF, Forner A, Korangy F, N'Kontchou G, Barget N, Ayuso C, Ormandy LA, Manns MP, Beaugrand M and Bruix J: A phase II open label trial evaluating safety and efficacy of a telomerase peptide vaccination in patients with advanced hepatocellular carcinoma. BMC Cancer. 10:2092010. View Article : Google Scholar : PubMed/NCBI
13	Kyte JA, Gaudernack G, Dueland S, Trachsel S, Julsrud L and Aamdal S: Telomerase peptide vaccination combined with temozolomide: A clinical trial in stage IV melanoma patients. Clin Cancer Res. 17:4568–4580. 2011. View Article : Google Scholar : PubMed/NCBI
14	Hunger RE, Lang K Kernland, Markowski CJ, Trachsel S, Møller M, Eriksen JA, Rasmussen AM, Braathen LR and Gaudernack G: Vaccination of patients with cutaneous melanoma with telomerase-specific peptides. Cancer Immunol Immunother. 60:1553–1564. 2011. View Article : Google Scholar : PubMed/NCBI
15	Kokhaei P, Palma M, Hansson L, Osterborg A, Mellstedt H and Choudhury A: Telomerase (hTERT 611–626) serves as a tumor antigen in B-cell chronic lymphocytic leukemia and generates spontaneously antileukemic, cytotoxic T cells. Exp Hematol. 35:297–304. 2007. View Article : Google Scholar : PubMed/NCBI
16	Choi J, Kim H, Kim Y, Jang M, Jeon J, Hwang YI, Shon WJ, Song YW, Kang JS and Lee WJ: The anti-inflammatory effect of GV1001 mediated by the downregulation of ENO1-induced pro-inflammatory cytokine production. Immune Netw. 15:291–303. 2015. View Article : Google Scholar : PubMed/NCBI
17	Chang JE, Kim HJ, Yi E, Jheon S and Kim K: Reduction of ischaemia-reperfusion injury in a rat lung transplantation model by low-concentration GV1001. Eur J Cardiothorac Surg. 50:972–979. 2016. View Article : Google Scholar : PubMed/NCBI
18	Koo TY, Yan JJ and Yang J: Protective effect of peptide GV1001 against renal ischemia-reperfusion injury in mice. Transplant Proc. 46:1117–1122. 2014; View Article : Google Scholar : PubMed/NCBI
19	Yaoita H, Ogawa K, Maehara K and Maruyama Y: Attenuation of ischemia/reperfusion injury in rats by a caspase inhibitor. Circulation. 97:276–281. 1998. View Article : Google Scholar : PubMed/NCBI
20	Shimamoto A, Chong AJ, Yada M, Shomura S, Takayama H, Fleisig AJ, Agnew ML, Hampton CR, Rothnie CL, Spring DJ, et al: Inhibition of Toll-like receptor 4 with eritoran attenuates myocardial ischemia-reperfusion injury. Circulation. 114 1 Suppl:I270–I274. 2006. View Article : Google Scholar : PubMed/NCBI
21	Arslan F, Smeets MB, O'Neill LA, Keogh B, McGuirk P, Timmers L, Tersteeg C, Hoefer IE, Doevendans PA, Pasterkamp G and de Kleijn DP: Myocardial ischemia/reperfusion injury is mediated by leukocytic Toll-like receptor-2 and reduced by systemic administration of a novel anti-Toll-like receptor-2 antibody. Circulation. 121:80–90. 2010. View Article : Google Scholar : PubMed/NCBI
22	Haskó G, Linden J, Cronstein B and Pacher P: Adenosine receptors: Therapeutic aspects for inflammatory and immune diseases. Nat Rev Drug Discov. 7:759–770. 2008. View Article : Google Scholar : PubMed/NCBI
23	Pitarys CJ II, Virmani R, Vildibill HD Jr, Jackson EK and Forman MB: Reduction of myocardial reperfusion injury by intravenous adenosine administered during the early reperfusion period. Circulation. 83:237–247. 1991. View Article : Google Scholar : PubMed/NCBI
24	Janier MF, Vanoverschelde JL and Bergmann SR: Adenosine protects ischemic and reperfused myocardium by receptor-mediated mechanisms. Am J Physiol. 264:H163–H170. 1993.PubMed/NCBI
25	Hausenloy DJ and Yellon DM: Myocardial ischemia-reperfusion injury: A neglected therapeutic target. J Clin Invest. 123:92–100. 2013. View Article : Google Scholar : PubMed/NCBI
26	Nian M, Lee P, Khaper N and Liu P: Inflammatory cytokines and postmyocardial infarction remodeling. Circ Res. 94:1543–1553. 2004. View Article : Google Scholar : PubMed/NCBI
27	Cao Z, Hu Y, Wu W, Ha T, Kelley J, Deng C, Chen Q, Li C, Li J and Li Y: The TIR/BB-loop mimetic AS-1 protects the myocardium from ischaemia/reperfusion injury. Cardiovasc Res. 84:442–451. 2009. View Article : Google Scholar : PubMed/NCBI
28	Disis ML: Mechanism of action of immunotherapy. Semin Oncol. 41 Suppl 5:S3–S13. 2014. View Article : Google Scholar : PubMed/NCBI
29	Mazzola P, Radhi S, Mirandola L, Annoni G, Jenkins M, Cobos E and Chiriva-Internati M: Aging, cancer, and cancer vaccines. Immun Ageing. 9:42012. View Article : Google Scholar : PubMed/NCBI
30	Martínez P and Blasco MA: Telomeric and extra-telomeric roles for telomerase and the telomere-binding proteins. Nat Rev Cancer. 11:161–176. 2011. View Article : Google Scholar : PubMed/NCBI
31	Choi I, Choi J, Kim J, Oh SY, Kim S and Lee E: AB0125 the effect of Gv1001, a peptide vaccine, in animal model of rheumatoid arthritis. Annals Rheumat Dis. 73:8452014. View Article : Google Scholar