Mdivi-1, a mitochondrial fission inhibitor, reduces angiotensin-II- induced hypertension by mediating VSMC phenotypic switch - 17/06/21
pages | 12 |
Iconographies | 7 |
Vidéos | 0 |
Autres | 0 |
Abstract |
Vascular smooth muscle cell (VSMC) phenotypic switch plays an essential role in the pathogenesis of hypertension. Mitochondrial dynamics, such as mitochondrial fission, can also contribute to VSMC phenotypic switch. Whether mitochondrial fission act as a novel target for anti-hypertensive drug development remains unknown. In the present study, we confirmed that angiotensin II (AngII) rapidly and continuously induced mitochondrial fission in VSMCs. We also detected the phosphorylation status of dynamin-related protein-1 (Drp1), a key protein involved in mitochondrial fission, at Ser616 site; and observed Drp1 mitochondrial translocation in VSMCs or arteries of AngII-induced hypertensive mice. The Drp1 inhibitor mitochondrial division inhibitor-1 (Mdivi-1) dramatically reversed AngII-induced Drp1 phosphorylation, mitochondrial fission, and reactive oxidative species generation. Treatment with Mdivi-1 (20 mg/kg/every other day) significantly attenuated AngII-induced hypertension (22 mmHg), arterial remodeling, and cardiac hypertrophy, in part by preventing VSMC phenotypic switch. In addition, Mdivi-1 treatment was not associated with liver or renal functional injury. Collectively, these results indicate that Mdivi-1 inhibited mitochondrial fission, recovered mitochondrial activity, and prevented AngII-induced VSMC phenotypic switch, resulting in reduced hypertension.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | Mitochondria fission is an integrated part in AngII-triggered VSMCs phenotypic switch. |
• | AngII promotes Drp1 phosphorylation at Ser616, and Drp1 mitochondrial translocation. |
• | Mdivi-1 supplementation inhibited AngII-induced VSMCs phenotypic switch, then attenuation hypertension. |
Keywords : Mitochondrial fission, Oxidative stress, Angiotensin II, Mdivi-1, VSMC phenotypic switch, Hypertension
Plan
Vol 140
Article 111689- août 2021 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’achat d’article à l’unité est indisponible à l’heure actuelle.
Déjà abonné à cette revue ?