Protective role of chaperone-mediated autophagy against atherosclerosis

Julio Madrigal-Matute, Jenny de Bruijn, Kim van Kuijk, Dario F Riascos-Bernal, Antonio Diaz, Inmaculada Tasset, Adrián Martín-Segura, Marion J.J. Gijbel, Bianca Sander, Susmita Kaushik, Erik A.L. Biessen, Simoni Tiano, Mathieu Bourdenx, Gregory J. Krause, Ian McCracken, Andrew H Baker, Jin Han, Nicholas Sibinga, Jose Javier Bravo-Cordero, Fernando MacianRajat Singh, Patrick C.N. Rensen, Jimmy F.P. Berbée, Gerard Pasterkamp, Judith Sluimer, Ana Maria Cuervo

Research output: Contribution to journalArticlepeer-review

Abstract

Chaperone-mediated autophagy (CMA) contributes to regulation of energy homeostasis by timely degradation of enzymes involved in glucose and lipid metabolism. Here, we report reduced CMA activity in vascular smooth muscle cells and macrophages in murine and human arteries in response to atherosclerotic challenges. We show that in vivo genetic blockage of CMA worsens
atherosclerotic pathology through both systemic and cell-autonomous changes in vascular smooth muscle cells and macrophages, the two main cell types involved in atherogenesis. CMA deficiency promotes dedifferentiation of vascular smooth muscle cells and a pro-inflammatory state in macrophages. Conversely, a genetic mouse model with upregulated CMA shows lower vulnerability to the pro-atherosclerotic challenge. We propose that CMA could be an attractive therapeutic target against cardiovascular diseases.
Original languageEnglish
JournalProceedings of the National Academy of Sciences
DOIs
Publication statusPublished - 1 Apr 2022

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