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microRNA-21-5p dysregulation in exosomes derived from heart failure patients impairs regenerative potential.

Publication ,  Journal Article
Qiao, L; Hu, S; Liu, S; Zhang, H; Ma, H; Huang, K; Li, Z; Su, T; Vandergriff, A; Tang, J; Allen, T; Dinh, P-U; Cores, J; Yin, Q; Li, Y; Cheng, K
Published in: J Clin Invest
April 29, 2019

Exosomes, as functional paracrine units of therapeutic cells, can partially reproduce the reparative properties of their parental cells. The constitution of exosomes, as well as their biological activity, largely depends on the cells that secrete them. We isolated exosomes from explant-derived cardiac stromal cells from patients with heart failure (FEXO) or from normal donor hearts (NEXO) and compared their regenerative activities in vitro and in vivo. Patients in the FEXO group exhibited an impaired ability to promote endothelial tube formation and cardiomyocyte proliferation in vitro. Intramyocardial injection of NEXO resulted in structural and functional improvements in a murine model of acute myocardial infarction. In contrast, FEXO therapy exacerbated cardiac function and left ventricular remodeling. microRNA array and PCR analysis revealed dysregulation of miR-21-5p in FEXO. Restoring miR-21-5p expression rescued FEXO's reparative function, whereas blunting miR-21-5p expression in NEXO diminished its therapeutic benefits. Further mechanistic studies revealed that miR-21-5p augmented Akt kinase activity through the inhibition of phosphatase and tensin homolog. Taken together, the heart failure pathological condition altered the miR cargos of cardiac-derived exosomes and impaired their regenerative activities. miR-21-5p contributes to exosome-mediated heart repair by enhancing angiogenesis and cardiomyocyte survival through the phosphatase and tensin homolog/Akt pathway.

Duke Scholars

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Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

April 29, 2019

Volume

129

Issue

6

Start / End Page

2237 / 2250

Location

United States

Related Subject Headings

  • Stromal Cells
  • Signal Transduction
  • Regeneration
  • Proto-Oncogene Proteins c-akt
  • Neovascularization, Physiologic
  • Myocytes, Cardiac
  • Myocardium
  • MicroRNAs
  • Mice
  • Male
 

Citation

APA
Chicago
ICMJE
MLA
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Qiao, L., Hu, S., Liu, S., Zhang, H., Ma, H., Huang, K., … Cheng, K. (2019). microRNA-21-5p dysregulation in exosomes derived from heart failure patients impairs regenerative potential. J Clin Invest, 129(6), 2237–2250. https://doi.org/10.1172/JCI123135
Qiao, Li, Shiqi Hu, Suyun Liu, Hui Zhang, Hong Ma, Ke Huang, Zhenhua Li, et al. “microRNA-21-5p dysregulation in exosomes derived from heart failure patients impairs regenerative potential.J Clin Invest 129, no. 6 (April 29, 2019): 2237–50. https://doi.org/10.1172/JCI123135.
Qiao L, Hu S, Liu S, Zhang H, Ma H, Huang K, et al. microRNA-21-5p dysregulation in exosomes derived from heart failure patients impairs regenerative potential. J Clin Invest. 2019 Apr 29;129(6):2237–50.
Qiao, Li, et al. “microRNA-21-5p dysregulation in exosomes derived from heart failure patients impairs regenerative potential.J Clin Invest, vol. 129, no. 6, Apr. 2019, pp. 2237–50. Pubmed, doi:10.1172/JCI123135.
Qiao L, Hu S, Liu S, Zhang H, Ma H, Huang K, Li Z, Su T, Vandergriff A, Tang J, Allen T, Dinh P-U, Cores J, Yin Q, Li Y, Cheng K. microRNA-21-5p dysregulation in exosomes derived from heart failure patients impairs regenerative potential. J Clin Invest. 2019 Apr 29;129(6):2237–2250.

Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

April 29, 2019

Volume

129

Issue

6

Start / End Page

2237 / 2250

Location

United States

Related Subject Headings

  • Stromal Cells
  • Signal Transduction
  • Regeneration
  • Proto-Oncogene Proteins c-akt
  • Neovascularization, Physiologic
  • Myocytes, Cardiac
  • Myocardium
  • MicroRNAs
  • Mice
  • Male