Chaperone-mediated autophagy protects against atherosclerosis

Atherosclerosis, the leading cause of cardiovascular death, is driven by hyperlipidemia, inflammation and aggravated by aging. As chaperone-mediated autophagy (CMA), a selective type of lysosomal degradation for intracellular proteins, diminishes with age and is inhibited by lipid excess, we studied...

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Bibliographic Details
Published in:Autophagy 2022-10, Vol.18 (10), p.2505-2507
Main Authors: Madrigal-Matute, Julio, Cuervo, Ana Maria, Sluimer, Judith C.
Format: Article
Language:English
Subjects:
Animals
Atherosclerosis - metabolism
Autophagic Punctum
Autophagy - physiology
Cardiovascular disease
Chaperone-Mediated Autophagy
cholesterol
Humans
inflammation
insulin
Lipids
lysosomes
Lysosomes - metabolism
macrophages
Mice
Mice, Transgenic
Molecular Chaperones - metabolism
smooth muscle cells
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Summary:Atherosclerosis, the leading cause of cardiovascular death, is driven by hyperlipidemia, inflammation and aggravated by aging. As chaperone-mediated autophagy (CMA), a selective type of lysosomal degradation for intracellular proteins, diminishes with age and is inhibited by lipid excess, we studied if the decline in CMA could contribute to atherosclerosis pathogenesis. We found that CMA declines in human and murine vasculature with disease progression. Inhibition and reactivation of CMA using transgenic mouse models establishes a protective effect of CMA against atherogenesis. CMA upregulation ameliorates both systemic metabolic parameters, and vascular cell function. Our work suggests CMA reactivation could be a viable therapeutic strategy to prevent and reduce cardiovascular disease.
ISSN:1554-8627
1554-8635
DOI:10.1080/15548627.2022.2096397