Elastogenesis Stimulation by Minoxidil or Nebivolol Reduces Premature Aging of the Aortic Wall in Diabetic Mice - Université de Picardie Jules Verne Accéder directement au contenu
Pré-Publication, Document De Travail Année : 2024

Elastogenesis Stimulation by Minoxidil or Nebivolol Reduces Premature Aging of the Aortic Wall in Diabetic Mice

Daniel Berrio
  • Fonction : Auteur
Eva Brauchle
  • Fonction : Auteur
Juergen Brinckmann
  • Fonction : Auteur
Heiko Steenbock
  • Fonction : Auteur
Vincent Durlarch
  • Fonction : Auteur
Sébastien Blaise
  • Fonction : Auteur

Résumé

Background The approximately fifteen-year reduction in life expectancy observed in diabetic patients, compared to non-diabetic individuals, is believed to be attributed to the early onset of cardiovascular diseases. Among the molecular actors involved in the occurrence of cardiovascular complications, the remodeling of elastic fibers (EFs) in favor of degradation rather than neosynthesis is significant. Objective This study aims to modulate the elastogenesis/elastolysis balance in the arterial wall of diabetic db/db mice (a diabetic model where the leptin receptor is deficient) to limit the premature aging of their EFs and aortic stiffening. Methods Mice are treated with two antihypertensive agents: minoxidil (an ATP-sensitive potassium (KATP) channel opener) or nebivolol (a β-blocker also active on KATP channels). The degree of wear and functionality of EF are assessed after these treatments. We complement this analysis by identifying molecular actors from smooth muscle cell cultures. Results Our data show that by applying these antihypertensive agents in cultured vascular smooth muscle cells in vitro and in diabetic mice, we efficiently stimulate elastogenesis and inhibit elastolysis. Therefore, treatments restore functional EFs and limit their degradation. This brings blood pressure values of diseased mice close to normal ones (as in unaffected mice). Elastogenesis pathway stimulation and elastolysis inhibition are induced by the opening of sensitive KATP channels and the regulation of the forkhead box transcription factor (FOXO1). Conclusion Monitoring these two pathways could, therefore, be sufficient to limit the premature aging of the aorta and to reduce the occurrence of hypertension, atherosclerosis, and aneurysms in diabetic patients.

Dates et versions

hal-04554030 , version 1 (22-04-2024)

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Auberi Henry, Laetitia Vanalderwiert, Amandine Wahart, Daniel Berrio, Eva Brauchle, et al.. Elastogenesis Stimulation by Minoxidil or Nebivolol Reduces Premature Aging of the Aortic Wall in Diabetic Mice. 2024. ⟨hal-04554030⟩
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