Protective role of chaperone-mediated autophagy against atherosclerosis.
atherosclerotic plaques
lipid challenge
lysosomes
proteolysis
vascular disease
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
05 04 2022
05 04 2022
Historique:
entrez:
1
4
2022
pubmed:
2
4
2022
medline:
16
4
2022
Statut:
ppublish
Résumé
Chaperone-mediated autophagy (CMA) contributes to regulation of energy homeostasis by timely degradation of enzymes involved in glucose and lipid metabolism. Here, we report reduced CMA activity in vascular smooth muscle cells and macrophages in murine and human arteries in response to atherosclerotic challenges. We show that in vivo genetic blockage of CMA worsens atherosclerotic pathology through both systemic and cell-autonomous changes in vascular smooth muscle cells and macrophages, the two main cell types involved in atherogenesis. CMA deficiency promotes dedifferentiation of vascular smooth muscle cells and a proinflammatory state in macrophages. Conversely, a genetic mouse model with up-regulated CMA shows lower vulnerability to proatherosclerotic challenges. We propose that CMA could be an attractive therapeutic target against cardiovascular diseases.
Identifiants
pubmed: 35363568
doi: 10.1073/pnas.2121133119
pmc: PMC9168839
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2121133119Subventions
Organisme : HHS | NIH | National Institute of General Medical Sciences (NIGMS)
ID : TGT32GM007288
Organisme : NIA NIH HHS
ID : R01 AG021904
Pays : United States
Organisme : British Heart Foundation
ID : RG/20/5/34796
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : R01 AI113919
Pays : United States
Organisme : HHS | NIH | National Institute on Aging (NIA)
ID : AG031782
Organisme : NHLBI NIH HHS
ID : R01 HL149921
Pays : United States
Organisme : British Heart Foundation
ID : CH/11/2/28733
Pays : United Kingdom
Organisme : NIDDK NIH HHS
ID : R01 DK098408
Pays : United States
Organisme : HHS | NIH | National Institute on Aging (NIA)
ID : AG021904
Organisme : NIA NIH HHS
ID : P01 AG031782
Pays : United States
Organisme : HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ID : DK098408
Organisme : NIA NIH HHS
ID : R37 AG021904
Pays : United States
Commentaires et corrections
Type : CommentIn
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