title: Effects of ACE2 deficiency on physical performance and physiological adaptations of cardiac and skeletal muscle to exercise.
abstract: The renin-angiotensin system (RAS) is related to physiological adaptations induced by exercise. Angiotensin-converting enzyme (ACE) 2 is a major regulator of the RAS in tissues, as it metabolizes angiotensin (Ang) II to Ang-(1-7). The aim of this study was to determine the effects of ACE2 deficiency on physical performance and physiological adaptations induced by voluntary running. Physical performance, body composition and plasma angiotensin levels, as well as tissue morphology and gene expression of RAS components in the left ventricle (LV) and skeletal muscle (gastrocnemius), were evaluated in ACE2-deficient (ACE2(-/y)) and wild-type (ACE2(+/y)) mice after 6 weeks of voluntary wheel running. ACE2(-/y) mice run less than ACE2(+/y) mice (19±4.7 vs. 26±12.6 revolutions per day × 100, P<0.01). The ACE2(+/y) group presented a lower fat mass (15±1.1%) and higher muscle mass (76.6±1.6%) after 6 weeks of voluntary running compared with the sedentary control group (fat mass: 18.3±2.1%; muscle mass: 72.7±2.2). However, no change in body composition was observed in ACE2(-/y) mice after exercise. Heart and skeletal muscle hypertrophy was observed only in trained ACE2(+/y) mice. Besides a small decrease in Ang I in ACE2(-/y) mice, plasma levels of angiotensin peptides remained unchanged by exercise or ACE2 deficiency. In the LV of trained animals, AT2 gene expression was higher in ACE2(+/y) compared with ACE2(-/y) mice. ACE2 deficiency leads to an increase in AT1 gene expression in skeletal muscle. ACE expression in soleus was increased in all exercised groups. ACE2 deficiency affects physical performance and impairs cardiac and skeletal muscle adaptations to exercise.
authors.affiliation: National Institute of Science and Technology in Nanobiopharmaceutics and Physiology and Biophysics Department, UFMG, Belo Horizonte, Brazil.|Cardiology Institute of Rio Grande do Sul, University Foundation of Cardiology, Porto Alegre, Brazil.
authors.forename: Daisy
authors.initials: D
authors.lastname: Motta-Santos
authors.affiliation: National Institute of Science and Technology in Nanobiopharmaceutics and Physiology and Biophysics Department, UFMG, Belo Horizonte, Brazil.|Cardiology Institute of Rio Grande do Sul, University Foundation of Cardiology, Porto Alegre, Brazil.
authors.forename: Robson Augusto Souza
authors.initials: RA
authors.lastname: Dos Santos
authors.affiliation: National Institute of Science and Technology in Nanobiopharmaceutics and Physiology and Biophysics Department, UFMG, Belo Horizonte, Brazil.|Cardiology Institute of Rio Grande do Sul, University Foundation of Cardiology, Porto Alegre, Brazil.
authors.forename: Marilene
authors.initials: M
authors.lastname: Oliveira
authors.affiliation: Max Delbruck Center for Molecular Medicine, Berlin, Germany.
authors.forename: Fatimunnisa
authors.initials: F
authors.lastname: Qadri
authors.affiliation: Attoquant Diagnostics, Vienna, Austria.
authors.forename: Marko
authors.initials: M
authors.lastname: Poglitsch
authors.affiliation: Max Delbruck Center for Molecular Medicine, Berlin, Germany.|Current address: School of Physiology and Pharmacology, University of Bristol, Bristol, UK.
authors.forename: Valentina
authors.initials: V
authors.lastname: Mosienko
authors.affiliation: Sports Center, Federal University of Ouro Preto, Ouro Preto, Brazil.
authors.forename: Lenice
authors.initials: L
authors.lastname: Kappes Becker
authors.affiliation: National Institute of Science and Technology in Nanobiopharmaceutics and Physiology and Biophysics Department, UFMG, Belo Horizonte, Brazil.|Cardiology Institute of Rio Grande do Sul, University Foundation of Cardiology, Porto Alegre, Brazil.
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Campagnole-Santos
authors.affiliation: IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Joseph
authors.initials: J
authors.lastname: M Penninger
authors.affiliation: National Institute of Science and Technology in Nanobiopharmaceutics and Physiology and Biophysics Department, UFMG, Belo Horizonte, Brazil.|Max Delbruck Center for Molecular Medicine, Berlin, Germany.
authors.forename: Natalia
authors.initials: N
authors.lastname: Alenina
authors.affiliation: National Institute of Science and Technology in Nanobiopharmaceutics and Physiology and Biophysics Department, UFMG, Belo Horizonte, Brazil.|Max Delbruck Center for Molecular Medicine, Berlin, Germany.|Charité-University Medicine Berlin, Berlin, Germany.|Institute for Biology, University of Lübeck, Lübeck, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
mesh_terms: D000222:Adaptation, Physiological; D000085962:Angiotensin-Converting Enzyme 2; D000809:Angiotensins / Q000097:blood; D000818:Animals; D015444:Exercise; D005080:Exercise Test; D006321:Heart / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000502:physiology*; D009206:Myocardium; D007703:Peptidyl-Dipeptidase A / Q000172:deficiency*
chemical_list: D000809:Angiotensins; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2