Abstract MP06: Mitochondrial Dynamics and Vascular Effects: Role of OPA1 in Hypertension
Background: Defects in mitochondrial dynamics have been associated with various disorders, including cardiovascular diseases. OPA1 is essential for mitochondrial inner membrane fusion and mutation in OPA1 is associated with autosomal dominant optic atrophy. Since OPA1 has been reported to be associated with cell apoptosis, cell proliferation, mitochondrial ATP synthesis, calcium homeostasis and reactive oxygen species (ROS) production, we investigated its role in vascular function and/or structure in physiological and pathological condition like hypertension.
Methods and Results: We used the heterozygous Opa1 mouse model carrying the recurrent Opa1 delTTAG mutation and OPA1 silencing in artery smooth muscle and endothelial cells. Electron microscopy revealed altered mitochondrial cristae structure in vascular smooth muscle cells and endothelial cells of Opa1+/- mice, 6 month-old Opa1+/- mice had a normal baseline blood pressure and vascular function (contraction and dilation). A chronic treatment with L-NAME induced hypertension in mice. Systolic blood pressure was significantly greater in Opa1+/- than in wild type (WT) mice. This was associated with a stronger reduction in endothelium-dependent relaxation to acetylcholine of resistance arteries in Opa1+/- than in WT animal. On the other hand, hypertension-induced wall hypertrophy in the aorta was absent in Opa1+/- in association with reduced proliferation and increased apoptosis of vascular cells.
Conclusions: Thus mitochondria alteration due to OPA1 down-regulation did not affect baseline blood pressure and vascular tone but induced an excessive elevation in blood pressure in hypertension. These results suggest for the first time that OPA1 may play an important role in protection of the vasculature in pathological conditions such as hypertension.
Author Disclosures: P. Nguyen: None. C. Grenier: None. E. Lelievre: None. L. Grimaud: None. E. Vessieres: None. E. Sarzi: None. D. Bonneau: None. P. Reynier: None. C. Fassot: None. G. Lenaers: None. D. Henrion: None. L. Loufrani: None.
- © 2015 by American Heart Association, Inc.