@article{5b14d278a0234809879c9901e6152d3f,
title = "Protective role of chaperone-mediated autophagy against atherosclerosis",
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.",
keywords = "CHOLESTEROL, DEATH, DEFICIENCY, DEGRADATION, INSULIN-RESISTANCE, MACROPHAGES, PLAQUES, PROTEIN, RECEPTOR, SMOOTH-MUSCLE-CELLS, atherosclerotic plaques, lipid challenge, lysosomes, proteolysis, vascular disease",
author = "Julio Madrigal-Matute and {de Bruijn}, Jenny and {van Kuijk}, Kim and Riascos-Bernal, {Dario F} and Antonio Diaz and Inmaculada Tasset and Adri{\'a}n Mart{\'i}n-Segura and Gijbels, {Marion J J} and Bianca Sander and Susmita Kaushik and Biessen, {Erik A L} and Simoni Tiano and Mathieu Bourdenx and Krause, {Gregory J} and Ian McCracken and Baker, {Andrew H} and Han Jin and Sibinga, {Nicholas E S} and Bravo-Cordero, {Jose Javier} and Fernando Macian and Rajat Singh and Rensen, {Patrick C N} and Berb{\'e}e, {Jimmy F P} and Gerard Pasterkamp and Sluimer, {Judith C} and Cuervo, {Ana Maria}",
note = "Funding Information: We thank Trea Streefland (Leiden University Medical Center) for her assistance with generating the lipid profiles, and Jacques Debets and Clairy Dinjens (Maastricht University Medical Center) for assistance with sectioning and immunohistochemistry. The GTEx Project used for the calculation of CMA scores was supported by the Common Fund of the Office of the Director of the NIH, and the Tabula Sapiens Project, used for the same purpose, was supported by Grant 2019-203354 from the Chan Zuckerberg Initiative DAF. This work was supported by NIH Grants AG021904 and DK098408 (to A.M.C.) and AG031782 (to A.M.C., R.S., J.J.B.-C., and F.M.), the Leducq Foundation Network (A15CVD04 to A.M.C. and J.C.S.), and a Dr. Dekker Senior Postdoc Fellowship from the Dutch Heart Foundation (2016T060 to J.C.S.). J.M.-M. was supported by a postdoctoral fellowship from the American Heart Association (17POST33650088), A.M.-S. by a Ramon Areces Postdoctoral Fellowship, and G.J.K. by TGT32GM007288 and T32GM007491. Funding Information: ACKNOWLEDGMENTS. We thank Trea Streefland (Leiden University Medical Center) for her assistance with generating the lipid profiles, and Jacques Debets and Clairy Dinjens (Maastricht University Medical Center) for assistance with sectioning and immunohistochemistry. The GTEx Project used for the calculation of CMA scores was supported by the Common Fund of the Office of the Director of the NIH, and the Tabula Sapiens Project, used for the same purpose, was supported by Grant 2019-203354 from the Chan Zuckerberg Initiative DAF. This work was supported by NIH Grants AG021904 and DK098408 (to A.M.C.) and AG031782 (to A.M.C., R.S., J.J.B.-C., and F.M.), the Leducq Foundation Network (A15CVD04 to A.M.C. and J.C.S.), and a Dr. Dekker Senior Postdoc Fellowship from the Dutch Heart Foundation (2016T060 to J.C.S.). J.M.-M. was supported by a postdoctoral fellowship from the American Heart Association (17POST33650088), A.M.-S. by a Ramon Areces Postdoctoral Fellowship, and G.J.K. by TGT32GM007288 and T32GM007491. Publisher Copyright: Copyright {\textcopyright} 2022 the Author(s).",
year = "2022",
month = apr,
day = "5",
doi = "10.1073/pnas.2121133119",
language = "English",
volume = "119",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "14",
}