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Journal article

Proteomic signature of dysfunctional circulating endothelial colony‐forming cells of young adults

Abstract:

Background
A subpopulation of endothelial progenitor cells called endothelial colony‐forming cells (ECFCs) may offer a platform for cellular assessment in clinical studies because of their remarkable angiogenic and expansion potentials in vitro. Despite endothelial cell function being influenced by cardiovascular risk factors, no studies have yet provided a comprehensive proteomic profile to distinguish functional (ie, more angiogenic and expansive cells) versus dysfunctional circulating ECFCs of young adults. The aim of this study was to provide a detailed proteomic comparison between functional and dysfunctional ECFCs.
Methods and Results
Peripheral blood ECFCs were isolated from 11 subjects (45% men, aged 27±5 years) using Ficoll density gradient centrifugation. ECFCs expressed endothelial and progenitor surface markers and displayed cobblestone‐patterned morphology with clonal and angiogenic capacities in vitro. ECFCs were deemed dysfunctional if <1 closed tube formed during the in vitro tube formation assay and proliferation rate was <20%. Hierarchical functional clustering revealed distinct ECFC proteomic signatures between functional and dysfunctional ECFCs with changes in cellular mechanisms involved in exocytosis, vesicle transport, extracellular matrix organization, cell metabolism, and apoptosis. Targeted antiangiogenic proteins in dysfunctional ECFCs included SPARC (secreted protein acidic and rich in cysteine), CD36 (cluster of differentiation 36), LUM (lumican), and PTX3 (pentraxin‐related protein PYX3).
Conclusions
Circulating ECFCs with impaired angiogenesis and expansion capacities have a distinct proteomic profile and significant phenotype changes compared with highly angiogenic endothelial cells. Impaired angiogenesis in dysfunctional ECFCs may underlie the link between endothelial dysfunction and cardiovascular disease risks in young adults.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1161/jaha.121.021119

Authors


More by this author
Institution:
University of Oxford
Division:
MSD
Sub department:
HS RDM Cardiovascular Medicine
Oxford college:
St Hugh's; St Hughs College
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
RDM
Sub department:
RDM Cardiovascular Medicine
Role:
Author
ORCID:
0000-0002-4978-8965


Publisher:
Wiley
Journal:
Journal of the American Heart Association More from this journal
Volume:
10
Issue:
15
Article number:
e021119
Publication date:
2021-07-19
Acceptance date:
2021-06-16
DOI:
EISSN:
2047-9980
Pmid:
34275329


Language:
English
Keywords:
Pubs id:
1187105
Local pid:
pubs:1187105
Deposit date:
2021-09-15

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