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Proteomic profiling of extracellular vesicles reveals additional diagnostic biomarkers for myocardial infarction compared to plasma alone

Gidlöf, Olof LU ; Evander, Mikael LU ; Rezeli, Melinda LU ; Marko-Varga, György LU ; Laurell, Thomas LU and Erlinge, David LU (2019) In Scientific Reports 9(1).
Abstract

Extracellular vesicles (EVs) are submicron, membrane-enclosed particles that are released from cells in various pathophysiological states. The molecular cargo of these vesicles is considered to reflect the composition of the cell of origin, and the EV proteome is therefore a potential source of biomarkers for various diseases. Our aim was to determine whether EVs isolated from plasma provide additional diagnostic value or improved pathophysiological understanding compared to plasma alone in the context of myocardial infarction (MI). A panel of proximity extension assays (n = 92) was employed to analyze EV lysates and plasma from patients with MI (n = 60) and healthy controls (n = 22). After adjustment for multiple comparisons, a total... (More)

Extracellular vesicles (EVs) are submicron, membrane-enclosed particles that are released from cells in various pathophysiological states. The molecular cargo of these vesicles is considered to reflect the composition of the cell of origin, and the EV proteome is therefore a potential source of biomarkers for various diseases. Our aim was to determine whether EVs isolated from plasma provide additional diagnostic value or improved pathophysiological understanding compared to plasma alone in the context of myocardial infarction (MI). A panel of proximity extension assays (n = 92) was employed to analyze EV lysates and plasma from patients with MI (n = 60) and healthy controls (n = 22). After adjustment for multiple comparisons, a total of 11 dysregulated proteins were identified in EVs of MI patients compared to the controls (q < 0.01). Three of these proteins: chymotrypsin C (CTRC), proto-oncogene tyrosine-protein kinase SRC (SRC) and C-C motif chemokine ligand 17 (CCL17) were unaltered in the corresponding plasma samples. As biomarkers for MI, rudimentary to no evidence exists for these proteins. In a separate group of patients with varying degrees of coronary artery disease, the decrease in EV-associated (but not plasma-related) SRC levels was confirmed by ELISA. Confirmation of the presence of SRC on EVs of different sizes and cellular origins was performed with ELISA, flow cytometry and nanoparticle tracking analysis. In conclusion, the data revealed that despite a similarity in the EV and plasma proteomes, analysis of isolated EVs does indeed provide additional diagnostic information that cannot be obtained from plasma alone.

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author
organization
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type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
9
issue
1
publisher
Nature Publishing Group
external identifiers
  • scopus:85067593583
ISSN
2045-2322
DOI
10.1038/s41598-019-45473-9
language
English
LU publication?
yes
id
c4dca4c0-5509-4535-ac6b-728c556f8812
date added to LUP
2019-07-03 12:09:32
date last changed
2019-07-30 05:05:53
@article{c4dca4c0-5509-4535-ac6b-728c556f8812,
  abstract     = {<p>Extracellular vesicles (EVs) are submicron, membrane-enclosed particles that are released from cells in various pathophysiological states. The molecular cargo of these vesicles is considered to reflect the composition of the cell of origin, and the EV proteome is therefore a potential source of biomarkers for various diseases. Our aim was to determine whether EVs isolated from plasma provide additional diagnostic value or improved pathophysiological understanding compared to plasma alone in the context of myocardial infarction (MI). A panel of proximity extension assays (n = 92) was employed to analyze EV lysates and plasma from patients with MI (n = 60) and healthy controls (n = 22). After adjustment for multiple comparisons, a total of 11 dysregulated proteins were identified in EVs of MI patients compared to the controls (q &lt; 0.01). Three of these proteins: chymotrypsin C (CTRC), proto-oncogene tyrosine-protein kinase SRC (SRC) and C-C motif chemokine ligand 17 (CCL17) were unaltered in the corresponding plasma samples. As biomarkers for MI, rudimentary to no evidence exists for these proteins. In a separate group of patients with varying degrees of coronary artery disease, the decrease in EV-associated (but not plasma-related) SRC levels was confirmed by ELISA. Confirmation of the presence of SRC on EVs of different sizes and cellular origins was performed with ELISA, flow cytometry and nanoparticle tracking analysis. In conclusion, the data revealed that despite a similarity in the EV and plasma proteomes, analysis of isolated EVs does indeed provide additional diagnostic information that cannot be obtained from plasma alone.</p>},
  articleno    = {8991},
  author       = {Gidlöf, Olof and Evander, Mikael and Rezeli, Melinda and Marko-Varga, György and Laurell, Thomas and Erlinge, David},
  issn         = {2045-2322},
  language     = {eng},
  month        = {06},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {Proteomic profiling of extracellular vesicles reveals additional diagnostic biomarkers for myocardial infarction compared to plasma alone},
  url          = {http://dx.doi.org/10.1038/s41598-019-45473-9},
  volume       = {9},
  year         = {2019},
}