Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
November-2016 Volume 14 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
November-2016 Volume 14 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Trimetazidine protects against cardiac ischemia/reperfusion injury via effects on cardiac miRNA‑21 expression, Akt and the Bcl‑2/Bax pathway

  • Authors:
    • Ning Ma
    • Jingyun Bai
    • Weihua Zhang
    • Hong Luo
    • Xin Zhang
    • Donghai Liu
    • Chenhui Qiao
  • View Affiliations / Copyright

    Affiliations: Department of Cardiovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
    Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4216-4222
    |
    Published online on: September 26, 2016
       https://doi.org/10.3892/mmr.2016.5773
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Trimetazidine is a piperazine-derived metabolic agent, which exerts cell protective effects and has been reported to be efficient in the treatment of chronic stable angina pectoris. In addition, it has been shown to exert protection against acute myocardial infarction. The present study aimed to investigate whether trimetazidine protects against cardiac ischemia/reperfusion (I/R) injury, and to determine whether its curative effects are associated with microRNA (miRNA)‑21 expression, Akt, and the B‑cell lymphoma 2 (Bcl‑2)/Bcl‑2‑associated X protein (Bax) pathway. Cardiac I/R injury was induced by ligating the left anterior descending coronary artery in adult rats. Subsequently, cardiac function was evaluated, and the expression levels of miRNA‑21, Bcl‑2, Bax and phosphorylated‑Akt were detected using quantitative polymerase chain reaction and western blotting. The results indicated that trimetazidine was able to significantly protect cardiac function and reduce infarct size in rats following cardiac I/R injury. Furthermore, trimetazidine significantly promoted miRNA‑21 expression and phosphorylated‑Akt protein expression, and reduced the Bcl‑2/Bax ratio in rats following cardiac I/R injury. Knockdown of miRNA‑21 using anti‑miR‑21 plasmids was able to reverse the protective effects of trimetazidine against cardiac I/R injury. These results indicated that miRNA‑21 serves a protective role in cardiac I/R injury via Akt and the Bcl‑2/Bax pathway. In addition, trimetazidine exerts protective effects against cardiac I/R injury through cardiac miRNA‑21 expression, Akt, and the Bcl‑2/Bax pathway. Therefore, the present study provided evidence regarding the protective effects of miRNA‑21 on cardiac I/R injury following treatment with trimetazidine in vivo.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

View References

1 

Xiao J, Li J, Xu T, Lv D, Shen B, Song Y and Xu J: Pregnancy-induced physiological hypertrophy protects against cardiac ischemia-reperfusion injury. Int J Clin Exp Pathol. 7:229–235. 2013.PubMed/NCBI

2 

Pisarenko OI, Lankin VZ, Konovalova GG, Serebryakova LI, Shulzhenko VS, Timoshin AA, Tskitishvili OV, Pelogeykina YA and Studneva IM: Apelin-12 and its structural analog enhance antioxidant defense in experimental myocardial ischemia and reperfusion. Mol Cell Biochem. 391:241–250. 2014. View Article : Google Scholar : PubMed/NCBI

3 

Liu LF, Qin Q, Qian ZH, Shi M, Deng QC, Zhu WP, Zhang H, Tao XM and Liu Y: Protective effects of melatonin on ischemia-reperfusion induced myocardial damage and hemodynamic recovery in rats. Eur Rev Med Pharmacol Sci. 18:3681–3686. 2014.PubMed/NCBI

4 

Lenčová-Popelová O, Jirkovský E, Mazurová Y, Lenčo J, Adamcová M, Šimůnek T, Geršl V and Štěrba M: Molecular remodeling of left and right ventricular myocardium in chronic anthracycline cardiotoxicity and post-treatment follow up. PLoS One. 9:e960552014. View Article : Google Scholar : PubMed/NCBI

5 

Chua CC, Gao J, Ho YS, Xu X, Kuo IC, Chua KY, Wang H, Hamdy RC, Reed JC and Chua BH: Over-expression of a modified bifunctional apoptosis regulator protects against cardiac injury and doxorubicin-induced cardiotoxicity in transgenic mice. Cardiovasc Res. 81:20–27. 2009. View Article : Google Scholar : PubMed/NCBI

6 

Wang Y, Zhang ZZ, Wu Y, Zhan J, He XH and Wang YL: Honokiol protects rat hearts against myocardial ischemia reperfusion injury by reducing oxidative stress and inflammation. Exp Ther Med. 5:315–319. 2013.PubMed/NCBI

7 

Mishra PK, Tyagi N, Kundu S and Tyagi SC: MicroRNAs are involved in homocysteine-induced cardiac remodeling. Cell Biochem Biophys. 55:153–162. 2009. View Article : Google Scholar : PubMed/NCBI

8 

Liu F, Yin L, Zhang L, Liu W, Liu J, Wang Y and Yu B: Trimetazidine improves right ventricular function by increasing miR-21 expression. Int J Mol Med. 30:849–855. 2012.PubMed/NCBI

9 

Ikeda S and Pu WT: Expression and function of microRNAs in heart disease. Curr Drug Targets. 11:913–925. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Opie LH and Boucher F: Trimetazidine and myocardial ischemic contracture in isolated rat heart. Am J Cardiol. 76:38B–40B. 1995. View Article : Google Scholar : PubMed/NCBI

11 

Kim JS, Kim CH, Chun KJ, Kim JH, Park YH, Kim J, Choi JH, Lee SH, Kim EJ, Yu DG, et al: Effects of trimetazidine in patients with acute myocardial infarction: Data from the Korean acute myocardial infarction registry. Clin Res Cardiol. 102:915–922. 2013. View Article : Google Scholar : PubMed/NCBI

12 

Hoda MN, Li W, Ahmad A, Ogbi S, Zemskova MA, Johnson MH, Ergul A, Hill WD, Hess DC and Sazonova IY: Sex-independent neuroprotection with minocycline after experimental thromboembolic stroke. Exp Transl Stroke Med. 3:162011. View Article : Google Scholar : PubMed/NCBI

13 

Hoda MN, Siddiqui S, Herberg S, Periyasamy-Thandavan S, Bhatia K, Hafez SS, Johnson MH, Hill WD, Ergul A, Fagan SC and Hess DC: Remote ischemic perconditioning is effective alone and in combination with intravenous tissue-type plasminogen activator in murine model of embolic stroke. Stroke. 43:2794–2799. 2012. View Article : Google Scholar : PubMed/NCBI

14 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

15 

Li X, Liu J, Lin L, Guo Y, Lin C, Zhang C and Yang B: Traditional Chinese medicine shuang shen ning xin attenuates myocardial ischemia/reperfusion injury by preserving of mitochondrial function. Evid Based Complement Alternat Med. 2014:1809652014. View Article : Google Scholar : PubMed/NCBI

16 

Qiao Z, Ma J and Liu H: Evaluation of the antioxidant potential of Salvia miltiorrhiza ethanol extract in a rat model of ischemia-reperfusion injury. Molecules. 16:10002–10012. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Shen B, Li J, Gao L, Zhang J and Yang B: Role of CC-chemokine receptor 5 on myocardial ischemia-reperfusion injury in rats. Mol Cell Biochem. 378:137–144. 2013. View Article : Google Scholar : PubMed/NCBI

18 

Ussher JR, Fillmore N, Keung W, Mori J, Beker DL, Wagg CS, Jaswal JS and Lopaschuk GD: Trimetazidine therapy prevents obesity-induced cardiomyopathy in mice. Can J Cardiol. 30:940–944. 2014. View Article : Google Scholar : PubMed/NCBI

19 

Allibardi S, Chierchia SL, Margonato V, Merati G, Neri G, Dell'Antonio G and Samaja M: Effects of trimetazidine on metabolic and functional recovery of postischemic rat hearts. Cardiovasc Drugs Ther. 12:543–549. 1998. View Article : Google Scholar : PubMed/NCBI

20 

Zhou J and Zhang J: Identification of miRNA-21 and miRNA-24 in plasma as potential early stage markers of acute cerebral infarction. Mol Med Rep. 10:971–976. 2014.PubMed/NCBI

21 

Duan X, Ji B, Wang X, Liu J, Zheng Z, Long C, Tang Y and Hu S: Expression of microRNA-1 and microRNA-21 in different protocols of ischemic conditioning in an isolated rat heart model. Cardiology. 122:36–43. 2012. View Article : Google Scholar : PubMed/NCBI

22 

Yin C, Wang X and Kukreja RC: Endogenous microRNAs induced by heat-shock reduce myocardial infarction following ischemia-reperfusion in mice. FEBS Lett. 582:4137–4142. 2008. View Article : Google Scholar : PubMed/NCBI

23 

Damania P, Sen B, Dar SB, Kumar S, Kumari A, Gupta E, Sarin SK and Venugopal SK: Hepatitis B virus induces cell proliferation via HBx-induced microRNA-21 in hepatocellular carcinoma by targeting programmed cell death protein4 (PDCD4) and phosphatase and tensin homologue (PTEN). PLoS One. 9:e917452014. View Article : Google Scholar : PubMed/NCBI

24 

Jansen F, Yang X, Proebsting S, Hoelscher M, Przybilla D, Baumann K, Schmitz T, Dolf A, Endl E, Franklin BS, et al: MicroRNA expression in circulating microvesicles predicts cardiovascular events in patients with coronary artery disease. J Am Heart Assoc. 3:e0012492014. View Article : Google Scholar : PubMed/NCBI

25 

Song JQ, Teng X, Cai Y, Tang CS and Qi YF: Activation of Akt/GSK-3beta signaling pathway is involved in intermedin(1–53) protection against myocardial apoptosis induced by ischemia/reperfusion. Apoptosis. 14:1299–1307. 2009. View Article : Google Scholar : PubMed/NCBI

26 

Zhang XJ, Xiong ZB, Tang AL, Ma H, Ma YD, Wu JG and Dong YG: Rosiglitazone-induced myocardial protection against ischaemia-reperfusion injury is mediated via a phosphatidylinositol 3-kinase/Akt-dependent pathway. Clin Exp Pharmacol Physiol. 37:156–161. 2010. View Article : Google Scholar : PubMed/NCBI

27 

Kutala VK, Khan M, Mandal R, Ganesan LP, Tridandapani S, Kalai T, Hideg K and Kuppusamy P: Attenuation of myocardial ischemia-reperfusion injury by trimetazidine derivatives functionalized with antioxidant properties. J Pharmacol Exp Ther. 317:921–928. 2006. View Article : Google Scholar : PubMed/NCBI

28 

Liu Z, Li Z and Liu X: Effect of ginsenoside Re on cardiomyocyte apoptosis and expression of Bcl-2/Bax gene after ischemia and reperfusion in rats. J Huazhong Univ Sci Technolog Med Sci. 22:305–309. 2002. View Article : Google Scholar : PubMed/NCBI

29 

Tian Y, Zhang W, Xia D, Modi P, Liang D and Wei M: Postconditioning inhibits myocardial apoptosis during prolonged reperfusion via a JAK2-STAT3-Bcl-2 pathway. J Biomed Sci. 18:532011. View Article : Google Scholar : PubMed/NCBI

30 

Khan M, Meduru S, Mostafa M, Khan S, Hideg K and Kuppusamy P: Trimetazidine, administered at the onset of reperfusion, ameliorates myocardial dysfunction and injury by activation of p38 mitogen-activated protein kinase and Akt signaling. J Pharmacol Exp Ther. 333:421–429. 2010. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Ma N, Bai J, Zhang W, Luo H, Zhang X, Liu D and Qiao C: Trimetazidine protects against cardiac ischemia/reperfusion injury via effects on cardiac miRNA‑21 expression, Akt and the Bcl‑2/Bax pathway. Mol Med Rep 14: 4216-4222, 2016.
APA
Ma, N., Bai, J., Zhang, W., Luo, H., Zhang, X., Liu, D., & Qiao, C. (2016). Trimetazidine protects against cardiac ischemia/reperfusion injury via effects on cardiac miRNA‑21 expression, Akt and the Bcl‑2/Bax pathway. Molecular Medicine Reports, 14, 4216-4222. https://doi.org/10.3892/mmr.2016.5773
MLA
Ma, N., Bai, J., Zhang, W., Luo, H., Zhang, X., Liu, D., Qiao, C."Trimetazidine protects against cardiac ischemia/reperfusion injury via effects on cardiac miRNA‑21 expression, Akt and the Bcl‑2/Bax pathway". Molecular Medicine Reports 14.5 (2016): 4216-4222.
Chicago
Ma, N., Bai, J., Zhang, W., Luo, H., Zhang, X., Liu, D., Qiao, C."Trimetazidine protects against cardiac ischemia/reperfusion injury via effects on cardiac miRNA‑21 expression, Akt and the Bcl‑2/Bax pathway". Molecular Medicine Reports 14, no. 5 (2016): 4216-4222. https://doi.org/10.3892/mmr.2016.5773
Copy and paste a formatted citation
x
Spandidos Publications style
Ma N, Bai J, Zhang W, Luo H, Zhang X, Liu D and Qiao C: Trimetazidine protects against cardiac ischemia/reperfusion injury via effects on cardiac miRNA‑21 expression, Akt and the Bcl‑2/Bax pathway. Mol Med Rep 14: 4216-4222, 2016.
APA
Ma, N., Bai, J., Zhang, W., Luo, H., Zhang, X., Liu, D., & Qiao, C. (2016). Trimetazidine protects against cardiac ischemia/reperfusion injury via effects on cardiac miRNA‑21 expression, Akt and the Bcl‑2/Bax pathway. Molecular Medicine Reports, 14, 4216-4222. https://doi.org/10.3892/mmr.2016.5773
MLA
Ma, N., Bai, J., Zhang, W., Luo, H., Zhang, X., Liu, D., Qiao, C."Trimetazidine protects against cardiac ischemia/reperfusion injury via effects on cardiac miRNA‑21 expression, Akt and the Bcl‑2/Bax pathway". Molecular Medicine Reports 14.5 (2016): 4216-4222.
Chicago
Ma, N., Bai, J., Zhang, W., Luo, H., Zhang, X., Liu, D., Qiao, C."Trimetazidine protects against cardiac ischemia/reperfusion injury via effects on cardiac miRNA‑21 expression, Akt and the Bcl‑2/Bax pathway". Molecular Medicine Reports 14, no. 5 (2016): 4216-4222. https://doi.org/10.3892/mmr.2016.5773
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team