RT Journal Article
SR Electronic
T1 Partial endothelial-to-mesenchymal transition (EndMT) contributes to lumen re-organization after carotid artery ligation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.08.13.456319
DO 10.1101/2021.08.13.456319
A1 Yamashiro, Yoshito
A1 Ramirez, Karina
A1 Nagayama, Kazuaki
A1 Tomita, Shuhei
A1 Kubota, Yoshiaki
A1 Yanagisawa, Hiromi
YR 2021
UL http://biorxiv.org/content/early/2021/08/14/2021.08.13.456319.abstract
AB Endothelial-to-mesenchymal transition (EndMT) is a fundamental process in vascular remodeling. Carotid artery ligation is commonly used for induction of neointima formation and vessel stenosis; however, the precise regulatory mechanism of vascular remodeling is not entirely understood. In this study, we showed that resident endothelial cells (ECs) are the origin of neointima cells and ECs transiently expressed CD45 in the early stage of neointima formation accompanied by increased expression of EndMT markers. In vitro, CD45-positive EndMT was induced by stabilization of HIF-1α with cobalt chloride or VHL inhibitor in human primary ECs, which mimicked the hypoxic condition of ligated artery, and promoted the formation of integrin α11-SHARPIN complex. Notably, a CD45 phosphatase inhibitor disrupted this complex, thereby destabilizing cell-cell junctions. These results suggest that the CD45 activity is required for the retention of an EC phenotype and cell-cell junctions during EndMT (termed “partial EndMT”). We thus propose a novel mechanism of partial EndMT that contributes to lumen re-organization during vascular injury.Competing Interest StatementThe authors have declared no competing interest.