Cytoglobin regulates blood pressure and vascular tone through nitric oxide metabolism in the vascular wall

Xiaoping Liu (), Mohamed A. El-Mahdy, James Boslett, Saradhadevi Varadharaj, Craig Hemann, Tamer M. Abdelghany, Raed S. Ismail, Sean C. Little, Danlei Zhou, Le Thi Thanh Thuy, Norifumi Kawada and Jay L. Zweier ()
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Xiaoping Liu: College of Medicine, The Ohio State University
Mohamed A. El-Mahdy: College of Medicine, The Ohio State University
James Boslett: College of Medicine, The Ohio State University
Saradhadevi Varadharaj: College of Medicine, The Ohio State University
Craig Hemann: College of Medicine, The Ohio State University
Tamer M. Abdelghany: College of Medicine, The Ohio State University
Raed S. Ismail: College of Medicine, The Ohio State University
Sean C. Little: College of Medicine, The Ohio State University
Danlei Zhou: College of Medicine, The Ohio State University
Le Thi Thanh Thuy: Graduate School of Medicine, Osaka City University
Norifumi Kawada: Graduate School of Medicine, Osaka City University
Jay L. Zweier: College of Medicine, The Ohio State University

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms14807

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