title: Genetic Deletion of ACE2 Induces Vascular Dysfunction in C57BL/6 Mice: Role of Nitric Oxide Imbalance and Oxidative Stress.
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.
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.|Laboratório de Reatividade Cardiovascular, Universidade Federal de Alagoas, Maceió, Alagoas, Brazil.|Instituto Nacional de Ciência e Tecnologia em NanoBiofarmacêutica (NanoBIOFAR).
authors.forename: Luiza A
authors.initials: LA
authors.lastname: Rabelo
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.|Instituto Nacional de Ciência e Tecnologia em NanoBiofarmacêutica (NanoBIOFAR).
authors.forename: Mihail
authors.initials: M
authors.lastname: Todiras
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.|Laboratório de Reatividade Cardiovascular, Universidade Federal de Alagoas, Maceió, Alagoas, Brazil.|Instituto Nacional de Ciência e Tecnologia em NanoBiofarmacêutica (NanoBIOFAR).
authors.forename: Valéria
authors.initials: V
authors.lastname: Nunes-Souza
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.|Charité University Medicine, Berlin, Germany.
authors.forename: Fatimunnisa
authors.initials: F
authors.lastname: Qadri
authors.affiliation: Nephrology/Intensive Care, Charité Campus Virchow Klinikum, Experimental and Clinical Research Center (ECRC), Berlin, Germany.
authors.forename: István András
authors.initials: IA
authors.lastname: Szijártó
authors.affiliation: Nephrology/Intensive Care, Charité Campus Virchow Klinikum, Experimental and Clinical Research Center (ECRC), Berlin, Germany.
authors.forename: Maik
authors.initials: M
authors.lastname: Gollasch
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Josef M
authors.initials: JM
authors.lastname: Penninger
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.|Instituto Nacional de Ciência e Tecnologia em NanoBiofarmacêutica (NanoBIOFAR).|Charité University Medicine, Berlin, Germany.|Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
authors.affiliation: Instituto Nacional de Ciência e Tecnologia em NanoBiofarmacêutica (NanoBIOFAR).|Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Robson A
authors.initials: RA
authors.lastname: Santos
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.|Instituto Nacional de Ciência e Tecnologia em NanoBiofarmacêutica (NanoBIOFAR).|Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Natalia
authors.initials: N
authors.lastname: Alenina
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001011:Aorta / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D015227:Lipid Peroxidation / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics; D014664:Vasodilation / Q000235:genetics
chemical_list: D000975:Antioxidants; D012333:RNA, Messenger; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D013482:Superoxide Dismutase; D007703:Peptidyl-Dipeptidase A; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2