| Title: |
Protective role of chaperone-mediated autophagy against atherosclerosis |
| Authors: |
Madrigal-Matute, J; de Bruijn, J; van Kuijk, K; Riascos-Bernal, DF; Diaz, A; Tasset, I; Martín-Segura, A; Gijbels, MJJ; Sander, B; Kaushik, S; Biessen, EAL; Tiano, S; Bourdenx, M; Krause, GJ; McCracken, I; Baker, AH; Jin, H; Sibinga, NES; Bravo-Cordero, JJ; Macian, F; Singh, R; Rensen, PCN; Berbée, JFP; Pasterkamp, G; Sluimer, JC; Cuervo, AM |
| Source: |
Proceedings of the National Academy of Sciences of the United States of America (PNAS) , 119 (14) , Article e2121133119. (2022) |
| Publisher Information: |
Proceedings of the National Academy of Sciences |
| Publication Year: |
2022 |
| Collection: |
University College London: UCL Discovery |
| Subject Terms: |
atherosclerotic plaques; lipid challenge; lysosomes; proteolysis; vascular disease; Animals; Atherosclerosis; Autophagy; Chaperone-Mediated Autophagy; Diabetes Mellitus; Type 2; Mice |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| Relation: |
https://discovery.ucl.ac.uk/id/eprint/10147197/1/pnsa.pdf; https://discovery.ucl.ac.uk/id/eprint/10147197/ |
| Availability: |
https://discovery.ucl.ac.uk/id/eprint/10147197/1/pnsa.pdf; https://discovery.ucl.ac.uk/id/eprint/10147197/ |
| Rights: |
open |
| Accession Number: |
edsbas.B3B2BEAA |
| Database: |
BASE |