Contribution of PDGFRα-positive cells in maintenance and injury responses in mouse large vessels

TY - JOUR

T1 - Contribution of PDGFRα-positive cells in maintenance and injury responses in mouse large vessels

AU - Kimura, Kenichi

AU - Ramirez, Karina

AU - Nguyen, Tram Anh Vu

AU - Yamashiro, Yoshito

AU - Sada, Aiko

AU - Yanagisawa, Hiromi

PY - 2021/4/21

Y1 - 2021/4/21

N2 - The maladaptive remodeling of vessel walls with neointima formation is a common feature of proliferative vascular diseases. It has been proposed that neointima formation is caused by the dedifferentiation of mature smooth muscle cells (SMCs). Recent evidence suggests that adventitial cells also participate in neointima formation; however, their cellular dynamics are not fully understood. In this study, we utilized a lineage tracing model of platelet-derived growth factor receptor alpha (PDGFRa) cells and examined cellular behavior during homeostasis and injury response. PDGFRa marked adventitial cells that were largely positive for Sca1 and a portion of medial SMCs, and both cell types were maintained for 2 years. Upon carotid artery ligation, PDGFRa-positive (+) cells were slowly recruited to the neointima and exhibited an immature SMC phenotype. In contrast, in a more severe wire denudation injury, PDGFRa+ cells were recruited to the neointima within 14 days and fully differentiated into SMCs. Under pressure overload induced by transverse aortic constriction, PDGFRa+ cells developed marked adventitial fibrosis. Taken together, our observations suggest that PDGFRa+ cells serve as a reservoir of adventitial cells and a subset of medial SMCs and underscore their context-dependent response to vascular injuries.

AB - The maladaptive remodeling of vessel walls with neointima formation is a common feature of proliferative vascular diseases. It has been proposed that neointima formation is caused by the dedifferentiation of mature smooth muscle cells (SMCs). Recent evidence suggests that adventitial cells also participate in neointima formation; however, their cellular dynamics are not fully understood. In this study, we utilized a lineage tracing model of platelet-derived growth factor receptor alpha (PDGFRa) cells and examined cellular behavior during homeostasis and injury response. PDGFRa marked adventitial cells that were largely positive for Sca1 and a portion of medial SMCs, and both cell types were maintained for 2 years. Upon carotid artery ligation, PDGFRa-positive (+) cells were slowly recruited to the neointima and exhibited an immature SMC phenotype. In contrast, in a more severe wire denudation injury, PDGFRa+ cells were recruited to the neointima within 14 days and fully differentiated into SMCs. Under pressure overload induced by transverse aortic constriction, PDGFRa+ cells developed marked adventitial fibrosis. Taken together, our observations suggest that PDGFRa+ cells serve as a reservoir of adventitial cells and a subset of medial SMCs and underscore their context-dependent response to vascular injuries.

KW - Adventitia/metabolism

KW - Animals

KW - Blood Vessels/injuries

KW - Cell Proliferation

KW - Homeostasis

KW - Male

KW - Mice

KW - Mice, Transgenic

KW - Neointima/metabolism

KW - Receptor, Platelet-Derived Growth Factor alpha/metabolism

U2 - 10.1038/s41598-021-88126-6

DO - 10.1038/s41598-021-88126-6

M3 - SCORING: Journal article

C2 - 33883668

VL - 11

SP - 8683

JO - SCI REP-UK

JF - SCI REP-UK

SN - 2045-2322

IS - 1

ER -