Journal article
Proteomic signature of dysfunctional circulating endothelial colony‐forming cells of young adults
- Abstract:
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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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- Files:
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(Preview, Version of record, 2.6MB, Terms of use)
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- Publisher copy:
- 10.1161/jaha.121.021119
Authors
- 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:
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2047-9980
- Pmid:
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34275329
- Language:
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English
- Keywords:
- Pubs id:
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1187105
- Local pid:
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pubs:1187105
- Deposit date:
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2021-09-15
Terms of use
- Copyright holder:
- Tan et al.
- Copyright date:
- 2021
- Rights statement:
- ©2021 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Licence:
- CC Attribution (CC BY)
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