Open AccessProtective role of chaperone-mediated autophagy against atherosclerosis
Author(s) -
Julio MadrigalMatute,
Jenny de Bruijn,
Kim van Kuijk,
Dario F. RiascosBernal,
Antonio Díaz,
Inmaculada Tasset,
Adrián MartínSegura,
Marion J. Gijbels,
Bianca Sander,
Susmita Kaushik,
Erik A.L. Biessen,
Simoni Tiano,
Mathieu Bourdenx,
Gregory J. Krause,
Ian R. McCracken,
Andrew H. Baker,
Han Jin,
Nicholas E.S. Sibinga,
Jose Javier Bravo-Cordero,
Fernando Macián,
Rajat Singh,
Patrick C.N. Rensen,
Jimmy F.P. Berbée,
Gérard Pasterkamp,
Judith C. Sluimer,
Ana María Cuervo
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2121133119
Subject(s) - autophagy , disease , diabetes mellitus , type 2 diabetes , medicine , atherosclerotic vascular disease , chaperone (clinical) , bioinformatics , biology , endocrinology , pathology , apoptosis , genetics
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.