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Arterioscler Thromb Vasc Biol. 2018 Jan;38(1):232-244. doi: 10.1161/ATVBAHA.117.309853. Epub 2017 Nov 30.

Adventitial Sca1+ Cells Transduced With ETV2 Are Committed to the Endothelial Fate and Improve Vascular Remodeling After Injury.

Author information

1
From the School of Cardiovascular Medicine & Sciences, King's College London British Heart Foundation Centre, London, United Kingdom.
2
From the School of Cardiovascular Medicine & Sciences, King's College London British Heart Foundation Centre, London, United Kingdom. qingbo.xu@kcl.ac.uk yanhua.hu@kcl.ac.uk.

Abstract

OBJECTIVE:

Vascular adventitial Sca1+ (stem cell antigen-1) progenitor cells preferentially differentiate into smooth muscle cells, which contribute to vascular remodeling and neointima formation in vessel grafts. Therefore, directing the differentiation of Sca1+ cells toward the endothelial lineage could represent a new therapeutic strategy against vascular disease.

APPROACH AND RESULTS:

We thus developed a fast, reproducible protocol based on the single-gene transfer of ETV2 (ETS variant 2) to differentiate Sca1+ cells toward the endothelial fate and studied the effect of cell conversion on vascular hyperplasia in a model of endothelial injury. After ETV2 transduction, Sca1+ adventitial cells presented a significant increase in the expression of early endothelial cell genes, including VE-cadherin, Flk-1, and Tie2 at the mRNA and protein levels. ETV2 overexpression also induced the downregulation of a panel of smooth muscle cell and mesenchymal genes through epigenetic regulations, by decreasing the expression of DNA-modifying enzymes ten-eleven translocation dioxygenases. Adventitial Sca1+ cells grafted on the adventitial side of wire-injured femoral arteries increased vascular wall hyperplasia compared with control arteries with no grafted cells. Arteries seeded with ETV2-transduced cells, on the contrary, showed reduced hyperplasia compared with control.

CONCLUSIONS:

These data give evidence that the genetic manipulation of vascular progenitors is a promising approach to improve vascular function after endothelial injury.

KEYWORDS:

adventitia; cell differentiation; stem cells; vascular diseases; vascular remodeling

PMID:
29191922
PMCID:
PMC5757665
DOI:
10.1161/ATVBAHA.117.309853
[Indexed for MEDLINE]
Free PMC Article

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