2. Academic Validation
  3. Potentiation of macrophage Piezo1 by atherogenic 7-ketocholesterol

Potentiation of macrophage Piezo1 by atherogenic 7-ketocholesterol

  • Cell Rep. 2025 Apr 22;44(4):115542. doi: 10.1016/j.celrep.2025.115542.
Edyta Glogowska 1,  Gregor P Jose 1,  Ana Rita Dias Araújo 1,  Malika Arhatte 1,  Raphael Divita 1,  Coraline Borowczyk 2,  Thibault Barouillet 2,  Baile Wang 3,  Frédéric Brau 1,  Rémi Peyronnet 4,  Amanda Patel 1,  Bruno Mesmin 1,  Takeshi Harayama 1,  Bruno Antonny 1,  Aimin Xu 3,  Laurent Yvan-Charvet 2,  Eric Honoré 5
Affiliations

Affiliations

  • 1 Université Côte d'Azur, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut de Pharmacologie Moléculaire et Cellulaire, Labex ICST, 06560 Valbonne, France.
  • 2 Institut National de la Santé et de la Recherche Médicale, Inserm, Université Côte d'Azur, Centre Méditerranéen de Médecine Moléculaire (C3M), Atip-Avenir, Fédération Hospitalo-Universitaire (FHU) Oncoage, Nice, France.
  • 3 State Key Laboratory of Pharmaceutical Biotechnology, Department of Medicine and Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong, China.
  • 4 Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg - Bad Krozingen, Medical Center - University of Freiburg and Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • 5 Université Côte d'Azur, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut de Pharmacologie Moléculaire et Cellulaire, Labex ICST, 06560 Valbonne, France; State Key Laboratory of Pharmaceutical Biotechnology, Department of Medicine and Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong, China. Electronic address: honore@ipmc.cnrs.fr.
PMID: 40215166 DOI: 10.1016/j.celrep.2025.115542
Abstract

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-/- 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.

Keywords

7-ketocholesterol; CP: Cell biology; CP: Metabolism; PUFAs; atherosclerosis; cholesterol; docosahexaenoic acid; ion channels; macrophage; mechanobiology; oxLDL; patch clamp.

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