CpG oligodeoxynucleotide preconditioning improves cardiac function after myocardial infarction via modulation of energy metabolism and angiogenesis

Deng Cheng Zhou, Yong Hui Su, Fu Qing Jiang, Jing Bo Xia, Hai Yan Wu, Zao Shang Chang, Wen Tao Peng, Guo Hua Song, Kyu Sang Park, Soo Ki Kim, Dong Qing Cai, Li Zheng, Xu Feng Qi

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Unmethylated CpG oligodeoxynucleotide (CpG-ODN), a Toll-like receptor 9 (TLR9) ligand, has been shown to protect against myocardial ischemia/reperfusion injury. However, the potential effects of CpG-ODN on myocardial infarction (MI) induced by persistent ischemia remains unclear. Here, we investigated whether and how CpG-ODN preconditioning protects against MI in mice. C57BL/6 mice were treated with CpG-ODN by i.p. injection 2 hr prior to MI induction, and cardiac function, and histology were analyzed 2 weeks after MI. Both 1826-CpG and KSK-CpG preconditioning significantly improved the left ventricular (LV) ejection fraction (LVEF) and LV fractional shortening (LVFS) when compared with non-CpG controls. Histological analysis further confirmed the cardioprotection of CpG-ODN preconditioning. In vitro studies further demonstrated that CpG-ODN preconditioning increases cardiomyocyte survival under hypoxic/ischemic conditions by enhancing stress tolerance through TLR9-mediated inhibition of the SERCA2/ATP and activation of AMPK pathways. Moreover, CpG-ODN preconditioning significantly increased angiogenesis in the infarcted myocardium compared with non-CpG. However, persistent TLR9 activation mediated by lentiviral infection failed to improve cardiac function after MI. Although CpG-ODN preconditioning increased angiogenesis in vitro, both the persistent stimulation of CpG-ODN and stable overexpression of TLR9 suppressed the tube formation of cardiac microvascular endothelial cells. CpG-ODN preconditioning significantly protects cardiac function against MI by suppressing the energy metabolism of cardiomyocytes and promoting angiogenesis. Our data also indicate that CpG-ODN preconditioning may be useful in MI therapy.

Original languageEnglish
Pages (from-to)4245-4257
Number of pages13
JournalJournal of Cellular Physiology
Volume233
Issue number5
DOIs
Publication statusPublished - 2018 May

Bibliographical note

Funding Information:
Foundation for Distinguished Young Talents in Higher Education of Guangdong Province, Grant number: 2013LYM0026; National Key R & D Program of China, Grant numbers: 2016YFE0204700, 2017YFA0103302; Guangdong Natural Science Funds for Distinguished Young Scholar, Guangdong, China, Grant number: 2014A030306011; New Star of Pearl River on Science and Technology of Guangzhou, Guangdong, China, Grant number: 2014J2200002; Top Young Talents of Guangdong Province Special Support Program, Guangdong, China, Grant number: 87315007; Guangdong Science and Technology Planning Project, Guangdong, China, Grant numbers: 2014A050503043, 2016A020221034; Fundamental Research Funds for the Central Universities, Grant number: 21617436; SRF for ROCS, SEM, China, Grant number: 2013-693; National Natural Science Foundation of China, Grant numbers: 81570222, 81770240, 91649203, 81670422, 8127018; Young

Funding Information:
Taishan Scholars Program of Shandong Province, Grant number: tsqn20161045

Funding Information:
This work was supported by grants from the National Key R and D Program of China (2016YFE0204700 and 2017YFA0103302), the National Natural Science Foundation of China (81570222, 81770240, 91649203, 81670422, and 81270183), the Guangdong Natural Science Funds for Distinguished Young Scholar (2014A030306011), the Guangdong Science and Technology Planning Project (2014A050503043 and 2016A020221034), the New Star of Pearl River on Science and Technology of Guangzhou (2014J2200002), the Top Young Talents of Guangdong Province Special Support Program (87315007), the Foundation for Distinguished Young Talents in Higher Education of Guangdong Province (2013LYM0026), the Fundamental Research Funds for the Central Universities (21617436), Young Taishan Scholars Program of Shandong Province (tsqn20161045) and the SRF for ROCS, SEM (2013-693), China.

Publisher Copyright:
© 2017 Wiley Periodicals, Inc.

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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