TY - JOUR
T1 - Adventitial MSC-like Cells Are Progenitors of Vascular Smooth Muscle Cells and Drive Vascular Calcification in Chronic Kidney Disease
AU - Kramann, Rafael
AU - Goettsch, Claudia
AU - Wongboonsin, Janewit
AU - Iwata, Hiroshi
AU - Schneider, Rebekka K.
AU - Kuppe, Christoph
AU - Kaesler, Nadine
AU - Chang-Panesso, Monica
AU - Machado, Flavia G.
AU - Gratwohl, Susannah
AU - Madhurima, Kaushal
AU - Hutcheson, Joshua D.
AU - Jain, Sanjay
AU - Aikawa, Elena
AU - Humphreys, Benjamin D.
N1 - Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/11/3
Y1 - 2016/11/3
N2 - Mesenchymal stem cell (MSC)-like cells reside in the vascular wall, but their role in vascular regeneration and disease is poorly understood. Here, we show that Gli1+ cells located in the arterial adventitia are progenitors of vascular smooth muscle cells and contribute to neointima formation and repair after acute injury to the femoral artery. Genetic fate tracing indicates that adventitial Gli1+ MSC-like cells migrate into the media and neointima during athero- and arteriosclerosis in ApoE−/− mice with chronic kidney disease. Our data indicate that Gli1+ cells are a major source of osteoblast-like cells during calcification in the media and intima. Genetic ablation of Gli1+ cells before induction of kidney injury dramatically reduced the severity of vascular calcification. These findings implicate Gli1+ cells as critical adventitial progenitors in vascular remodeling after acute and during chronic injury and suggest that they may be relevant therapeutic targets for mitigation of vascular calcification.
AB - Mesenchymal stem cell (MSC)-like cells reside in the vascular wall, but their role in vascular regeneration and disease is poorly understood. Here, we show that Gli1+ cells located in the arterial adventitia are progenitors of vascular smooth muscle cells and contribute to neointima formation and repair after acute injury to the femoral artery. Genetic fate tracing indicates that adventitial Gli1+ MSC-like cells migrate into the media and neointima during athero- and arteriosclerosis in ApoE−/− mice with chronic kidney disease. Our data indicate that Gli1+ cells are a major source of osteoblast-like cells during calcification in the media and intima. Genetic ablation of Gli1+ cells before induction of kidney injury dramatically reduced the severity of vascular calcification. These findings implicate Gli1+ cells as critical adventitial progenitors in vascular remodeling after acute and during chronic injury and suggest that they may be relevant therapeutic targets for mitigation of vascular calcification.
UR - http://www.scopus.com/inward/record.url?scp=84994803382&partnerID=8YFLogxK
U2 - 10.1016/j.stem.2016.08.001
DO - 10.1016/j.stem.2016.08.001
M3 - Article
C2 - 27618218
AN - SCOPUS:84994803382
SN - 1934-5909
VL - 19
SP - 628
EP - 642
JO - Cell Stem Cell
JF - Cell Stem Cell
IS - 5
ER -