3,4-dimethoxychalcone induces autophagy and reduces neointimal hyperplasia and aortic lesions in mouse models of atherosclerosis - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue (Data Paper) Cell Death and Disease Année : 2023

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

Carlota Alvarez-Lucena
Yanhua Hu
  • Fonction : Auteur
Guo Chen
Omar Motiño
Lisardo Boscá
Qingbo Xu
Oliver Kepp

Résumé

Abstract 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.
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Dates et versions

hal-04596685 , version 1 (31-05-2024)

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Giulia Cerrato, Carlota Alvarez-Lucena, Allan Sauvat, Yanhua Hu, Sabrina Forveille, et al.. 3,4-dimethoxychalcone induces autophagy and reduces neointimal hyperplasia and aortic lesions in mouse models of atherosclerosis. Cell Death and Disease, 2023, 14 (11), pp.758. ⟨10.1038/s41419-023-06305-x⟩. ⟨hal-04596685⟩
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