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Adventitial Sca1+ Cells Transduced with ETV2 Are Committed to the Endothelial Fate and Improve Vascular Remodeling after Injury

Research output: Contribution to journalArticlepeer-review

Original languageEnglish
Pages (from-to)232-244
Number of pages13
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume38
Issue number1
DOIs
Accepted/In press15 Nov 2017
Published1 Jan 2018

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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.

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