MicroRNA-210 as a novel therapy for treatment of ischemic heart disease

Shijun Hu, Mei Huang, Zongjin Li, Fangjun Jia, Zhumur Ghosh, Maarten A. Lijkwan, Pasquale Fasanaro, Ning Sun, Xi Wang, Fabio Martelli, Robert C. Robbins, Joseph C. Wu

Research output: Contribution to journalArticle

Abstract

Background-: MicroRNAs are involved in various critical functions, including the regulation of cellular differentiation, proliferation, angiogenesis, and apoptosis. We hypothesize that microRNA-210 can rescue cardiac function after myocardial infarction by upregulation of angiogenesis and inhibition of cellular apoptosis in the heart. Methods and results-: Using microRNA microarrays, we first showed that microRNA-210 was highly expressed in live mouse HL-1 cardiomyocytes compared with apoptotic cells after 48 hours of hypoxia exposure. We confirmed by polymerase chain reaction that microRNA-210 was robustly induced in these cells. Gain-of-function and loss-of-function approaches were used to investigate microRNA-210 therapeutic potential in vitro. After transduction, microRNA-210 can upregulate several angiogenic factors, inhibit caspase activity, and prevent cell apoptosis compared with control. Afterward, adult FVB mice underwent intramyocardial injections with minicircle vector carrying microRNA-210 precursor, minicircle carrying microRNA-scramble, or sham surgery. At 8 weeks, echocardiography showed a significant improvement of left ventricular fractional shortening in the minicircle vector carrying microRNA-210 precursor group compared with the minicircle carrying microRNA-scramble control. Histological analysis confirmed decreased cellular apoptosis and increased neovascularization. Finally, 2 potential targets of microRNA-210, Efna3 and Ptp1b, involved in angiogenesis and apoptosis were confirmed through additional experimental validation. Conclusion-: MicroRNA-210 can improve angiogenesis, inhibit apoptosis, and improve cardiac function in a murine model of myocardial infarction. It represents a potential novel therapeutic approach for treatment of ischemic heart disease.

Original languageEnglish
JournalCirculation
Volume122
Issue number11 SUPPL. 1
DOIs
Publication statusPublished - Sep 14 2010

Fingerprint

MicroRNAs
Myocardial Ischemia
Apoptosis
Therapeutics
Up-Regulation
Myocardial Infarction
Angiogenesis Inducing Agents
Caspases
Cardiac Myocytes
Echocardiography
Cell Proliferation

Keywords

  • gene therapy
  • ischemic heart disease
  • microRNA
  • minicircle vector

ASJC Scopus subject areas

  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine
  • Medicine(all)

Cite this

Hu, S., Huang, M., Li, Z., Jia, F., Ghosh, Z., Lijkwan, M. A., ... Wu, J. C. (2010). MicroRNA-210 as a novel therapy for treatment of ischemic heart disease. Circulation, 122(11 SUPPL. 1). https://doi.org/10.1161/CIRCULATIONAHA.109.928424

MicroRNA-210 as a novel therapy for treatment of ischemic heart disease. / Hu, Shijun; Huang, Mei; Li, Zongjin; Jia, Fangjun; Ghosh, Zhumur; Lijkwan, Maarten A.; Fasanaro, Pasquale; Sun, Ning; Wang, Xi; Martelli, Fabio; Robbins, Robert C.; Wu, Joseph C.

In: Circulation, Vol. 122, No. 11 SUPPL. 1, 14.09.2010.

Research output: Contribution to journalArticle

Hu, S, Huang, M, Li, Z, Jia, F, Ghosh, Z, Lijkwan, MA, Fasanaro, P, Sun, N, Wang, X, Martelli, F, Robbins, RC & Wu, JC 2010, 'MicroRNA-210 as a novel therapy for treatment of ischemic heart disease', Circulation, vol. 122, no. 11 SUPPL. 1. https://doi.org/10.1161/CIRCULATIONAHA.109.928424
Hu S, Huang M, Li Z, Jia F, Ghosh Z, Lijkwan MA et al. MicroRNA-210 as a novel therapy for treatment of ischemic heart disease. Circulation. 2010 Sep 14;122(11 SUPPL. 1). https://doi.org/10.1161/CIRCULATIONAHA.109.928424
Hu, Shijun ; Huang, Mei ; Li, Zongjin ; Jia, Fangjun ; Ghosh, Zhumur ; Lijkwan, Maarten A. ; Fasanaro, Pasquale ; Sun, Ning ; Wang, Xi ; Martelli, Fabio ; Robbins, Robert C. ; Wu, Joseph C. / MicroRNA-210 as a novel therapy for treatment of ischemic heart disease. In: Circulation. 2010 ; Vol. 122, No. 11 SUPPL. 1.
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AU - Fasanaro, Pasquale

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AB - Background-: MicroRNAs are involved in various critical functions, including the regulation of cellular differentiation, proliferation, angiogenesis, and apoptosis. We hypothesize that microRNA-210 can rescue cardiac function after myocardial infarction by upregulation of angiogenesis and inhibition of cellular apoptosis in the heart. Methods and results-: Using microRNA microarrays, we first showed that microRNA-210 was highly expressed in live mouse HL-1 cardiomyocytes compared with apoptotic cells after 48 hours of hypoxia exposure. We confirmed by polymerase chain reaction that microRNA-210 was robustly induced in these cells. Gain-of-function and loss-of-function approaches were used to investigate microRNA-210 therapeutic potential in vitro. After transduction, microRNA-210 can upregulate several angiogenic factors, inhibit caspase activity, and prevent cell apoptosis compared with control. Afterward, adult FVB mice underwent intramyocardial injections with minicircle vector carrying microRNA-210 precursor, minicircle carrying microRNA-scramble, or sham surgery. At 8 weeks, echocardiography showed a significant improvement of left ventricular fractional shortening in the minicircle vector carrying microRNA-210 precursor group compared with the minicircle carrying microRNA-scramble control. Histological analysis confirmed decreased cellular apoptosis and increased neovascularization. Finally, 2 potential targets of microRNA-210, Efna3 and Ptp1b, involved in angiogenesis and apoptosis were confirmed through additional experimental validation. Conclusion-: MicroRNA-210 can improve angiogenesis, inhibit apoptosis, and improve cardiac function in a murine model of myocardial infarction. It represents a potential novel therapeutic approach for treatment of ischemic heart disease.

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