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Protective role of chaperone-mediated autophagy against atherosclerosis

Madrigal-Matute, J; de Bruijn, J; van Kuijk, K; Riascos-Bernal, DF; Diaz, A; Tasset, I; Martín-Segura, A; ... Cuervo, AM; + view all (2022) Protective role of chaperone-mediated autophagy against atherosclerosis. Proceedings of the National Academy of Sciences of the United States of America (PNAS) , 119 (14) , Article e2121133119. 10.1073/pnas.2121133119. Green open access

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Abstract

Significance Cardiovascular diseases remain the leading cause of death worldwide, with atherosclerosis being the most common source of clinical events. Metabolic changes with aging associate with concurrent increased risk of both type 2 diabetes and cardiovascular disease, with the former further raising the risk of the latter. The activity of a selective type of autophagy, chaperone-mediated autophagy (CMA), decreases with age or upon dietary excesses. Here we study whether reduced CMA activity increases risk of atherosclerosis in mouse models. We have identified that CMA is up-regulated early in response to proatherogenic challenges and demonstrate that reduced systemic CMA aggravates vascular pathology in these conditions. We also provide proof-of-concept support that CMA up-regulation is an effective intervention to reduce atherosclerosis severity and progression.

Type: Article
Title: Protective role of chaperone-mediated autophagy against atherosclerosis
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1073/pnas.2121133119
Publisher version: https://doi.org/10.1073/pnas.2121133119
Language: English
Additional information: This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
Keywords: atherosclerotic plaques, lipid challenge, lysosomes, proteolysis, vascular disease, Animals, Atherosclerosis, Autophagy, Chaperone-Mediated Autophagy, Diabetes Mellitus, Type 2, Lysosomes, Mice
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > UK Dementia Research Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
URI: https://discovery.ucl.ac.uk/id/eprint/10147197
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