Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • 100th Anniversary of Insulin's Discovery (Jan 2021)
    • Hypoxia-inducible factors in disease pathophysiology and therapeutics (Oct 2020)
    • Latency in Infectious Disease (Jul 2020)
    • Immunotherapy in Hematological Cancers (Apr 2020)
    • Big Data's Future in Medicine (Feb 2020)
    • Mechanisms Underlying the Metabolic Syndrome (Oct 2019)
    • Reparative Immunology (Jul 2019)
    • View all review series ...
  • Viewpoint
  • Collections
    • Recently published
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • Recently published
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
microRNA-21-5p dysregulation in exosomes derived from heart failure patients impairs regenerative potential
Li Qiao, … , Yongjun Li, Ke Cheng
Li Qiao, … , Yongjun Li, Ke Cheng
Published April 29, 2019
Citation Information: J Clin Invest. 2019;129(6):2237-2250. https://doi.org/10.1172/JCI123135.
View: Text | PDF
Research Article Cardiology Stem cells

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

  • Text
  • PDF
Abstract

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.

Authors

Li Qiao, Shiqi Hu, Suyun Liu, Hui Zhang, Hong Ma, Ke Huang, Zhenhua Li, Teng Su, Adam Vandergriff, Junnan Tang, Tyler Allen, Phuong-Uyen Dinh, Jhon Cores, Qi Yin, Yongjun Li, Ke Cheng

×

Figure 8

miR-21-5p targets the PTEN pathway in post-MI pathology.

Options: View larger image (or click on image) Download as PowerPoint
miR-21-5p targets the PTEN pathway in post-MI pathology.
(A) Representat...
(A) Representative Western blot images showing the expression of various PTEN/Akt pathway components. (B–E) Quantitation of the levels of PTEN, p-Akt, t-Akt, Bcl-2, and caspase-3 (n = 3). (F) Representative Western blot images showing the expression of PCNA (proliferation marker), VEGF, and PDCD4 (miR-21 target). (G and H) Quantitation of the levels of PCNA, VEGF, and PDCD4 (n = 3). (B–I) All miR-21 groups were normalized to the relevant scrambled controls. *P < 0.05 compared to scrambled control. **P < 0.01 compared to scrambled control. ***P < 0.001 compared to scrambled control. NS, no significance compared to scrambled control. Two-tailed t test. All values are mean ± SD. (J) Schematic showing the working model of our study. CM/H9C2/EC/CF +miR-scr, HCs/H9C2 cells/HUVECs/human cardiac fibroblasts transfected with scrambled miR. CM/H9C2/EC/CF + miR-21, HCs/H9C2 cells/HUVECs/human cardiac fibroblasts transfected with miR-21-5p mimic.
Follow JCI:
Copyright © 2021 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts