title: Cytoglobin regulates blood pressure and vascular tone through nitric oxide metabolism in the vascular wall.
abstract: The identity of the specific nitric oxide dioxygenase (NOD) that serves as the main in vivo regulator of O2-dependent NO degradation in smooth muscle remains elusive. Cytoglobin (Cygb) is a recently discovered globin expressed in fibroblasts and smooth muscle cells with unknown function. Cygb, coupled with a cellular reducing system, efficiently regulates the rate of NO consumption by metabolizing NO in an O2-dependent manner with decreased NO consumption in physiological hypoxia. Here we show that Cygb is a major regulator of NO degradation and cardiovascular tone. Knockout of Cygb greatly prolongs NO decay, increases vascular relaxation, and lowers blood pressure and systemic vascular resistance. We further demonstrate that downregulation of Cygb prevents angiotensin-mediated hypertension. Thus, Cygb has a critical role in the regulation of vascular tone and disease. We suggest that modulation of the expression and NOD activity of Cygb represents a strategy for the treatment of cardiovascular disease.
authors.affiliation: Davis Heart and Lung Research Institute and Division of Cardiovascular Medicine, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Liu
authors.affiliation: Davis Heart and Lung Research Institute and Division of Cardiovascular Medicine, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: El-Mahdy
authors.affiliation: Davis Heart and Lung Research Institute and Division of Cardiovascular Medicine, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: James
authors.initials: J
authors.lastname: Boslett
authors.affiliation: Davis Heart and Lung Research Institute and Division of Cardiovascular Medicine, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Saradhadevi
authors.initials: S
authors.lastname: Varadharaj
authors.affiliation: Davis Heart and Lung Research Institute and Division of Cardiovascular Medicine, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Craig
authors.initials: C
authors.lastname: Hemann
authors.affiliation: Davis Heart and Lung Research Institute and Division of Cardiovascular Medicine, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Tamer M
authors.initials: TM
authors.lastname: Abdelghany
authors.affiliation: Davis Heart and Lung Research Institute and Division of Cardiovascular Medicine, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Raed S
authors.initials: RS
authors.lastname: Ismail
authors.affiliation: Davis Heart and Lung Research Institute and Division of Cardiovascular Medicine, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Sean C
authors.initials: SC
authors.lastname: Little
authors.affiliation: Davis Heart and Lung Research Institute and Division of Cardiovascular Medicine, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Danlei
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Department of Hepatology, Graduate School of Medicine, Osaka City University, Asahimachi 1-4-3, Abenoku, Osaka 545-8585, Japan.
authors.forename: Le Thi Thanh
authors.initials: LT
authors.lastname: Thuy
authors.affiliation: Department of Hepatology, Graduate School of Medicine, Osaka City University, Asahimachi 1-4-3, Abenoku, Osaka 545-8585, Japan.
authors.forename: Norifumi
authors.initials: N
authors.lastname: Kawada
authors.affiliation: Davis Heart and Lung Research Institute and Division of Cardiovascular Medicine, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Jay L
authors.initials: JL
authors.lastname: Zweier
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000517:prevention & control; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D000078842:Cytoglobin / Q000235:genetics / Q000502:physiology*; D015536:Down-Regulation; D005260:Female; D055785:Gene Knockdown Techniques; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009129:Muscle Tonus / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010105:Oxygenases / Q000378:metabolism; D051381:Rats; D017539:Tunica Intima / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D014655:Vascular Resistance / Q000502:physiology; D014664:Vasodilation / Q000502:physiology
chemical_list: D000078842:Cytoglobin; D009569:Nitric Oxide; D010105:Oxygenases; C114415:nitric oxide dioxygenase; D052250:Nitric Oxide Synthase Type III; D006152:Cyclic GMP