Potentiation of macrophage Piezo1 by atherogenic 7-ketocholesterol
The mechanosensitive ion channel Piezo1 present in endothelial and smooth muscle cells, as well as in macrophages, is emerging as a novel, important player in the etiology of atherosclerosis. Here, we show that myeloid-specific deficiency of Piezo1 in atherogenic Ldlr<sup>-/-</sup> mice reduces plaque formation. Moreover, chronic oxLDL, as well as its main oxysterol 7-ketocholesterol (7-KC), promotes Piezo1 opening by pressure stimulation in both mouse macrophages and transfected HEK cells. 7-KC dramatically enhances Piezo1 current amplitude and slows down inactivation and deactivation. This up-modulation involves an increase in Piezo1 expression, as well as a potentiation of mechanical gating that depends on membrane cholesterol depletion and decreased order. By contrast, Piezo1 is inhibited by the athero-protective free docosahexaenoic acid, either without or with 7-KC. Altogether, these findings indicate that macrophage Piezo1 is differentially modulated by pro- and anti-atherogenic lipids, pointing to the role of Piezo1 and its potentiation by oxysterols in atherosclerosis.
Authors
- Rémi Peyronnet (ORCID: https://orcid.org/0000-0002-5708-6410)
- Bruno Antonny (ORCID: https://orcid.org/0000-0002-9166-8668)
- Thibault Barouillet (ORCID: https://orcid.org/0009-0006-0157-3523)
- Gregor P. Jose (ORCID: https://orcid.org/0000-0001-6303-2286)
- T. HARAYAMA (ORCID: https://orcid.org/0000-0003-2255-4197)
- Ana Rita Dias Araújo (ORCID: https://orcid.org/0000-0003-3729-747X)
- Bruno Mesmin (ORCID: https://orcid.org/0000-0002-5437-3246)
- Edyta Glogowska (ORCID: https://orcid.org/0000-0001-7989-9466)
- Aimin Xu (ORCID: https://orcid.org/0000-0002-0668-033X)
- Malika Arhatte
- Baile Wang (ORCID: https://orcid.org/0000-0002-8080-2964)
- Laurent Yvan‐Charvet (ORCID: https://orcid.org/0000-0002-7748-4942)
- Éric Honoré (ORCID: https://orcid.org/0000-0002-8007-0919)
- Coraline Borowczyk (ORCID: https://orcid.org/0000-0002-0193-6578)
- Amanda J. Patel
- Frédéric Brau
- Raphael Divita
Institutions
- Inserm (FR)
- University of Freiburg (DE)
- Université Côte d'Azur (FR)
- Fédération Hospitalo-Universitaire, Paris Center for Microbiome Medicine (FR)
- Centre Méditerranéen de Médecine Moléculaire (FR)
- Universitäts-Herzzentrum Freiburg-Bad Krozingen (DE)
- Institut de Pharmacologie Moléculaire et Cellulaire (FR)
- University of Hong Kong (HK)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-04-01
- DOI
- https://doi.org/10.1016/j.celrep.2025.115542
- Citations
- 3
- Primary Topic
- Erythrocyte Function and Pathophysiology
- Type
- article
- Field-Weighted Citation Impact
- 3.49