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. Gijbels, Bianca Sander, Susmita Kaushik, Erik A.L. Biessen, Simoni Tiano, Mathieu Bourdenx, Gregory J. Krause, Ian McCracken, Andrew H. Baker, Han Jin, Nicholas E.S. Sibinga, Jose Javier Bravo-Cordero, Fernando MacianRajat Singh, Patrick C.N. Rensen, Jimmy F.P. Berbeé, Gerard Pasterkamp, Judith C. Sluimer, Ana Maria Cuervo

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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 proinflammatory state in macrophages. Conversely, a genetic mouse model with up-regulated CMA shows lower vulnerability to proatherosclerotic challenges. We propose that CMA could be an attractive therapeutic target against cardiovascular diseases.

Original languageEnglish (US)
Article numbere2121133119
JournalProceedings of the National Academy of Sciences of the United States of America
Volume119
Issue number14
DOIs
StatePublished - Apr 5 2022

Keywords

  • atherosclerotic plaques
  • lipid challenge
  • lysosomes
  • proteolysis
  • vascular disease

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Protective role of chaperone-mediated autophagy against atherosclerosis'. Together they form a unique fingerprint.

Cite this