Pré-Publication, Document De Travail Année : 2025

Hyperglycemia worsens smooth muscle foam cell formation through PI3Kγ-dependent defective autophagy

Résumé

ABSTRACT Background Diabetes significantly increases the risk of cardiovascular complications, particularly through the mechanisms of atherosclerosis. In this context, uncontrolled hyperglycaemia is a key contributor to arterial dysfunctions. However, the specific effects of elevated glucose levels on smooth muscle cells (SMC)-derived foam cells formation remain poorly defined. Methods Using a wire injury-based accelerated atherosclerosis mouse model combined to lipid biochemistry and cellular lipid imaging approaches, we analysed molecular mechanisms involved in SMC derived foam cell formation. Results Our findings demonstrated that hyperglycaemia induced a specific lipid loading in SMC in an accelerated atherosclerosis mice model. In vitro , high glucose concentration negatively affected autophagic process independently of lipid uptake and efflux in human and mouse primary SMC. Consistently, treatment with autophagy activators successfully reduced lipid droplet formation. Mechanistically, we identified that PI3Kψ activity impaired autophagy through TFEB phosphorylation promoting SMC foam cells formation in response to high glucose. Conclusion These findings shed light on the mechanisms underlying SMC homeostasis disruption under hyperglycemic conditions and underscore the potential therapeutic window for PI3Kψ inhibitor in managing cardiovascular diseases in diabetic patients.

Fichier non déposé

Dates et versions

hal-05348719 , version 1 (05-11-2025)

Identifiants

Citer

Labrana Honora, Wahart Amandine, Cormier Kévin, Solinhac Romain, Swiader Audrey, et al.. Hyperglycemia worsens smooth muscle foam cell formation through PI3Kγ-dependent defective autophagy. 2025. ⟨hal-05348719⟩
34 Consultations
0 Téléchargements

Altmetric

Partager

  • More