Pathological angiogenesis in retinopathy engages cellular senescence and is amenable to therapeutic elimination via BCL-xL inhibition.
Animals
Apoptosis
/ drug effects
Cellular Senescence
/ drug effects
Collagen Type I, alpha 1 Chain
/ metabolism
Cyclin-Dependent Kinase Inhibitor p16
/ deficiency
Disease Models, Animal
Endothelial Cells
/ cytology
Female
Flavonols
/ chemistry
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neovascularization, Pathologic
Retinal Diseases
/ drug therapy
Tacrolimus
/ analogs & derivatives
bcl-X Protein
/ antagonists & inhibitors
BCL-xL
UBX1967
aging
angiogenesis
cellular senescence
diabetes
p16(INK4A)
retina
retinopathy
senolytic
Journal
Cell metabolism
ISSN: 1932-7420
Titre abrégé: Cell Metab
Pays: United States
ID NLM: 101233170
Informations de publication
Date de publication:
06 04 2021
06 04 2021
Historique:
received:
27
07
2020
revised:
30
10
2020
accepted:
11
01
2021
pubmed:
7
2
2021
medline:
27
1
2022
entrez:
6
2
2021
Statut:
ppublish
Résumé
Attenuating pathological angiogenesis in diseases characterized by neovascularization such as diabetic retinopathy has transformed standards of care. Yet little is known about the molecular signatures discriminating physiological blood vessels from their diseased counterparts, leading to off-target effects of therapy. We demonstrate that in contrast to healthy blood vessels, pathological vessels engage pathways of cellular senescence. Senescent (p16
Identifiants
pubmed: 33548171
pii: S1550-4131(21)00011-5
doi: 10.1016/j.cmet.2021.01.011
pii:
doi:
Substances chimiques
AP20187
0
Collagen Type I, alpha 1 Chain
0
Cyclin-Dependent Kinase Inhibitor p16
0
Flavonols
0
bcl-X Protein
0
fisetin
OO2ABO9578
Tacrolimus
WM0HAQ4WNM
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
818-832.e7Subventions
Organisme : CIHR
ID : 148460
Pays : Canada
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests At the time of this work, P.R.T., R.D.R., S.Y.C., T.D., S.R.R., R.O., S.A., C.B.Y., D.M., and P.J.B. were employees of UNITY Biotechnology. P.S. is a consultant for UNITY Biotechnology. The rest of the authors declare no competing interests.