title: Red Blood Cell Function and Dysfunction: Redox Regulation, Nitric Oxide Metabolism, Anemia.
abstract: Recent clinical evidence identified anemia to be correlated with severe complications of cardiovascular disease (CVD) such as bleeding, thromboembolic events, stroke, hypertension, arrhythmias, and inflammation, particularly in elderly patients. The underlying mechanisms of these complications are largely unidentified. Recent Advances: Previously, red blood cells (RBCs) were considered exclusively as transporters of oxygen and nutrients to the tissues. More recent experimental evidence indicates that RBCs are important interorgan communication systems with additional functions, including participation in control of systemic nitric oxide metabolism, redox regulation, blood rheology, and viscosity. In this article, we aim to revise and discuss the potential impact of these noncanonical functions of RBCs and their dysfunction in the cardiovascular system and in anemia.
  
  
  
  The mechanistic links between changes of RBC functional properties and cardiovascular complications related to anemia have not been untangled so far.
  
  
  
  To allow a better understanding of the complications associated with anemia in CVD, basic and translational science studies should be focused on identifying the role of noncanonical functions of RBCs in the cardiovascular system and on defining intrinsic and/or systemic dysfunction of RBCs in anemia and its relationship to CVD both in animal models and clinical settings. Antioxid. Redox Signal. 26, 718-742.
authors.affiliation: 1 Cardiovascular Research Laboratory, Division of Cardiology, Pneumology, and Vascular Medicine, Medical Faculty, Heinrich Heine University of Düsseldorf , Düsseldorf, Germany .
authors.forename: Viktoria
authors.initials: V
authors.lastname: Kuhn
authors.affiliation: 1 Cardiovascular Research Laboratory, Division of Cardiology, Pneumology, and Vascular Medicine, Medical Faculty, Heinrich Heine University of Düsseldorf , Düsseldorf, Germany .
authors.forename: Lukas
authors.initials: L
authors.lastname: Diederich
authors.affiliation: 2 Department of Molecular Physiology and Biological Physics, Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine , Charlottesville, Virginia.
authors.forename: T C Stevenson
authors.initials: TCS
authors.lastname: Keller
authors.affiliation: 1 Cardiovascular Research Laboratory, Division of Cardiology, Pneumology, and Vascular Medicine, Medical Faculty, Heinrich Heine University of Düsseldorf , Düsseldorf, Germany .
authors.forename: Christian M
authors.initials: CM
authors.lastname: Kramer
authors.affiliation: 1 Cardiovascular Research Laboratory, Division of Cardiology, Pneumology, and Vascular Medicine, Medical Faculty, Heinrich Heine University of Düsseldorf , Düsseldorf, Germany .
authors.forename: Wiebke
authors.initials: W
authors.lastname: Lückstädt
authors.affiliation: 1 Cardiovascular Research Laboratory, Division of Cardiology, Pneumology, and Vascular Medicine, Medical Faculty, Heinrich Heine University of Düsseldorf , Düsseldorf, Germany .
authors.forename: Christina
authors.initials: C
authors.lastname: Panknin
authors.affiliation: 1 Cardiovascular Research Laboratory, Division of Cardiology, Pneumology, and Vascular Medicine, Medical Faculty, Heinrich Heine University of Düsseldorf , Düsseldorf, Germany .
authors.forename: Tatsiana
authors.initials: T
authors.lastname: Suvorava
authors.affiliation: 2 Department of Molecular Physiology and Biological Physics, Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine , Charlottesville, Virginia.
authors.forename: Brant E
authors.initials: BE
authors.lastname: Isakson
authors.affiliation: 1 Cardiovascular Research Laboratory, Division of Cardiology, Pneumology, and Vascular Medicine, Medical Faculty, Heinrich Heine University of Düsseldorf , Düsseldorf, Germany .
authors.forename: Malte
authors.initials: M
authors.lastname: Kelm
authors.affiliation: 1 Cardiovascular Research Laboratory, Division of Cardiology, Pneumology, and Vascular Medicine, Medical Faculty, Heinrich Heine University of Düsseldorf , Düsseldorf, Germany .
authors.forename: Miriam M
authors.initials: MM
authors.lastname: Cortese-Krott
mesh_terms: D000740:Anemia / Q000378:metabolism*; D000818:Animals; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D010084:Oxidation-Reduction
chemical_list: D009569:Nitric Oxide
keywords: RBC deformability; anemia; cardiovascular disease; hemolysis; nitric oxide; red blood cells; red cell eNOS