Role of mitochondrial dynamics in aortic aneurysm - 18/05/21
Résumé |
Introduction |
Aortic aneurysm rupture and dissection have a mortality rate of 75% due to hemorrhage. Their consequences seem well known, unlike their etiology, especially concerning anatomical damages along the aorta (ascending/descending thoracic aorta and abdominal aorta). Mitochondrial dysfunction is implicated in neurological, ophthalmic and cardiac pathologies, but mitochondrial dynamics, regulating mitochondrial functions, is still under-investigated in aortic diseases.
Objective |
To improve our understanding of aneurysm pathology, we investigated mitochondrial dynamics, according to the anatomical aorta locations.
Methods |
We used an aneurysm murine model [6 months old of hypertensive ldlr-/− male mice (angiotensin II, 1mg/kg/day) associated with hypercholesterolemic diet (HCD) for 28 days] to study mitochondrial dynamics. On the other hand, 6 months old opa1± hypertensive male mice were used to study aortic remodeling. Aortic mice segments were studied by histomorphometric analyzes (Orcein, Oil Red O and Sirius red staining), RT-qPCR and Western blot.
Results |
Ldlr-/− mice suffering from an abdominal aortic aneurysm showed a significant decrease in gene and protein expression of mitochondrial dynamics actors: Mitofusin 1/2, Drp1 and Fis1. In addition, our results demonstrated strong aneurysmal adventitial remodeling in supra-renal abdominal aorta in opa1± hypertensive mice with a significant increase of Mmp2/Timp2 ratio in gene and protein expression involved in aneurysm remodeling. Those results were associated with a significant decrease in smooth muscle cell contraction gene and proteins expression, indicating a phenotypic cell switch, promoting aneurysm formation.
Conclusion |
These data suggest that mitochondrial dynamics dysfunction associated with hypertensive condition are implicated in abdominal aortic aneurysm development.
Le texte complet de cet article est disponible en PDF.Plan
Vol 13 - N° 2
P. 185-186 - mai 2021 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.