3,4-dimethoxychalcone induces autophagy and reduces neointimal hyperplasia and aortic lesions in mouse models of atherosclerosis.

Autor: Cerrato G; Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute, Villejuif, France.; Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Paris, France., Alvarez-Lucena C; Instituto de Investigaciones Biomédicas 'Alberto Sols' (CSIC-UAM) and Centro de Investigación en Red en Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain., Sauvat A; Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute, Villejuif, France.; Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Paris, France., Hu Y; The Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, China., Forveille S; Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute, Villejuif, France.; Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Paris, France., Chen G; Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute, Villejuif, France.; Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Paris, France.; State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, Tianjin Key Laboratory of Protein Science, Haihe Laboratory of Cell Ecosystem, College of Life Sciences, Nankai University, Tianjin, China., Durand S; Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute, Villejuif, France.; Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Paris, France., Aprahamian F; Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute, Villejuif, France.; Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Paris, France., Leduc M; Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute, Villejuif, France.; Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Paris, France., Motiño O; Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute, Villejuif, France.; Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Paris, France., Boscá L; Instituto de Investigaciones Biomédicas 'Alberto Sols' (CSIC-UAM) and Centro de Investigación en Red en Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain., Xu Q; The Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, China., Kepp O; Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute, Villejuif, France. captain.olsen@gmail.com.; Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Paris, France. captain.olsen@gmail.com., Kroemer G; Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute, Villejuif, France. kroemer@orange.fr.; Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Paris, France. kroemer@orange.fr.; Institut du Cancer Paris CARPEM, Department of Biology, Hôpital Européen Georges Pompidou, AP-HP, Paris, France. kroemer@orange.fr.
Jazyk: angličtina
Zdroj: Cell death & disease [Cell Death Dis] 2023 Nov 22; Vol. 14 (11), pp. 758. Date of Electronic Publication: 2023 Nov 22.
DOI: 10.1038/s41419-023-06305-x
Abstrakt: Autophagy inducers can prevent cardiovascular aging and age-associated diseases including atherosclerosis. Therefore, we hypothesized that autophagy-inducing compounds that act on atherosclerosis-relevant cells might have a protective role in the development of atherosclerosis. Here we identified 3,4-dimethoxychalcone (3,4-DC) as an inducer of autophagy in several cell lines from endothelial, myocardial and myeloid/macrophagic origin, as demonstrated by the aggregation of the autophagosome marker GFP-LC3 in the cytoplasm of cells, as well as the downregulation of its nuclear pool indicative of autophagic flux. In this respect, 3,4-DC showed a broader autophagy-inducing activity than another chalcone (4,4- dimethoxychalcone), spermidine and triethylene tetramine. Thus, we characterized the potential antiatherogenic activity of 3,4-DC in two different mouse models, namely, (i) neointima formation with smooth muscle expansion of vein segments grafted to the carotid artery and (ii) genetically predisposed ApoE -/- mice fed an atherogenic diet. In the vein graft model, local application of 3,4-DC was able to maintain the lumen of vessels and to reduce neointima lesions. In the diet-induced model, intraperitoneal injections of 3,4-DC significantly reduced the number of atherosclerotic lesions in the aorta. In conclusion, 3,4-DC stands out as an autophagy inducer with potent antiatherogenic activity.
(© 2023. The Author(s).)
Databáze: MEDLINE
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