Cardiac Extracellular Vesicles (EVs) Released in the Presence or Absence of Inflammatory Cues Support Angiogenesis in Different Manners

Cells release extracellular vesicles (EVs) to communicate in a paracrine manner with other cells, and thereby influence processes, such as angiogenesis. The conditioned medium of human cardiac-derived adherent proliferating (CardAP) cells was recently shown to enhance angiogenesis. To elucidate whet...

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Bibliographic Details
Published in:International journal of molecular sciences 2019-12, Vol.20 (24), p.6363
Main Authors: Beez, Christien Madlen, Schneider, Maria, Haag, Marion, Pappritz, Kathleen, Van Linthout, Sophie, Sittinger, Michael, Seifert, Martina
Format: Article
Language:English
Subjects:
Angiogenesis
Animals
Biosynthesis
Blood Vessels - metabolism
Cardiomyocytes
CD63 antigen
Cell Line
Cells, Cultured
Centrifugation
Communication
Cues
Cytokines
Cytokines - metabolism
Endothelial cells
Endothelial Cells - metabolism
Extracellular vesicles
Extracellular Vesicles - metabolism
Flow cytometry
Growth factors
Heart
Humans
Inflammation
Inflammation Mediators - metabolism
Interleukin 6
Interleukin 8
Lymphocytes
Mice
MicroRNAs - genetics
MicroRNAs - metabolism
miRNA
Myocardium - cytology
Myocardium - metabolism
Paracrine signalling
Polymerase chain reaction
Proteins
Tetraspanin 30 - metabolism
Tumor necrosis factor-TNF
Vascular endothelial growth factor
Vascular Endothelial Growth Factor A - metabolism
Vesicles
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Summary:Cells release extracellular vesicles (EVs) to communicate in a paracrine manner with other cells, and thereby influence processes, such as angiogenesis. The conditioned medium of human cardiac-derived adherent proliferating (CardAP) cells was recently shown to enhance angiogenesis. To elucidate whether their released EVs are involved, we isolated them by differential centrifugation from the conditioned medium derived either in the presence or absence of a pro-inflammatory cytokine cocktail. Murine recipient cells internalized CardAP-EVs as determined by an intracellular detection of human proteins, such as CD63, by a novel flow cytometry method for studying EV-cell interaction. Moreover, endothelial cells treated for 24 h with either unstimulated or cytokine stimulated CardAP-EVs exhibited a higher tube formation capability on Matrigel. Interestingly, unstimulated CardAP-EVs caused endothelial cells to release significantly more vascular endothelial growth factor and interleukin (IL)-6, while cytokine stimulated CardAP-EVs significantly enhanced the release of IL-6 and IL-8. By nCounter miRNA expression assay (NanoString Technologies) we identified microRNA 302d-3p to be enhanced in unstimulated CardAP-EVs compared to their cytokine stimulated counterparts, which was verified by quantitative polymerase chain reaction. This study demonstrates that both CardAP-EVs are pro-angiogenic by inducing different factors from endothelial cells. This would allow to select potent targets for a safe and efficient therapeutic application.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms20246363