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Genetic deletion of ACE2 induces vascular dysfunction in C57BL/6 mice: role of nitric oxide imbalance and oxidative stress

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Item Type:Article
Title:Genetic deletion of ACE2 induces vascular dysfunction in C57BL/6 mice: role of nitric oxide imbalance and oxidative stress
Creators Name:Rabelo, L.A. and Todiras, M. and Nunes-Souza, V. and Qadri, F. and Szijártó, I.A. and Gollasch, M. and Penninger, J.M. and Bader, M. and Santos, R.A. and Alenina, N.
Abstract:Accumulating evidence indicates that angiotensin-converting enzyme 2 (ACE2) plays a critical role in cardiovascular homeostasis, and its altered expression is associated with major cardiac and vascular disorders. The aim of this study was to evaluate the regulation of vascular function and assess the vascular redox balance in ACE2-deficient (ACE2-/y) animals. Experiments were performed in 20-22 week-old C57BL/6 and ACE2-/y male mice. Evaluation of endothelium-dependent and -independent relaxation revealed an impairment of in vitro and in vivo vascular function in ACE2-/y mice. Drastic reduction in eNOS expression at both protein and mRNA levels, and a decrease in •NO concentrations were observed in aortas of ACE2-/y mice in comparison to controls. Consistently, these mice presented a lower plasma and urine nitrite concentration, confirming reduced •NO availability in ACE2-deficient animals. Lipid peroxidation was significantly increased and superoxide dismutase activity was decreased in aorta homogenates of ACE2-/y mice, indicating impaired antioxidant capacity. Taken together, our data indicate, that ACE2 regulates vascular function by modulating nitric oxide release and oxidative stress. In conclusion, we elucidate mechanisms by which ACE2 is involved in the maintenance of vascular homeostasis. Furthermore, these findings provide insights into the role of the renin-angiotensin system in both vascular and systemic redox balance.
Keywords:Antioxidants, Aorta, Gene Deletion, Inbred C57BL Mice, Lipid Peroxidation, Messenger RNA, Nitric Oxide, Nitric Oxide Synthase Type III, Oxidation-Reduction, Oxidative Stress, Peptidyl-Dipeptidase A, Renin-Angiotensin System, Superoxide Dismutase, Vascular Endothelium, Vasodilation, Animals, Mice
Source:PLoS ONE
Publisher:Public Library of Science
Page Range:e0150255
Date:12 April 2016
Official Publication:https://doi.org/10.1371/journal.pone.0150255
PubMed:View item in PubMed

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