Single-cell RNA-seq reveals a critical role of novel pro-inflammatory EndMT in mediating adverse remodeling in coronary artery-on-a-chip.
Sci Adv
; 7(34)2021 08.
Article
en En
| MEDLINE
| ID: mdl-34417174
ABSTRACT
A three-dimensional microengineered human coronary artery-on-a-chip was developed for investigation of the mechanism by which low and oscillatory shear stress (OSS) induces pro-atherogenic changes. Single-cell RNA sequencing revealed that OSS induced distinct changes in endothelial cells (ECs) including pro-inflammatory endothelial-to-mesenchymal transition (EndMT). OSS promoted pro-inflammatory EndMT through the Notch1/p38 MAPK-NF-κB signaling axis. Moreover, OSS-induced EC phenotypic changes resulted in proliferation and extracellular matrix (ECM) protein up-regulation in smooth muscle cells (SMCs) through the RANTES-mediated paracrine mechanism. IL-37 suppressed OSS-induced pro-inflammatory EndMT and thereby abrogated SMC proliferation and ECM protein remodeling. Overall, this study provides insights into endothelial heterogeneity under atheroprone shear stress and identifies the mechanistic role of a novel EC subtype in promoting adverse vascular remodeling. Further, this study demonstrates that anti-inflammatory approach is capable of mitigating vascular pathobiology evoked by atheroprone shear stress.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Vasos Coronarios
/
Células Endoteliales
Límite:
Humans
Idioma:
En
Revista:
Sci Adv
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos