Endothelial nitric oxide synthase in red blood cells: key to a new erythrocrine function?
Red blood cells (RBC) have been considered almost exclusively as a transporter of metabolic gases and nutrients for the tissues. It is an accepted dogma that RBCs take up and inactivate endothelium-derived NO via rapid reaction with oxyhemoglobin to form methemoglobin and nitrate, thereby limiting NO available for vasodilatation. Yet it has also been shown that RBCs not only act as "NO sinks", but exert an erythrocrine function - i.e an endocrine function of RBC - by synthesizing, transporting and releasing NO metabolic products and ATP, thereby potentially controlling systemic NO bioavailability and vascular tone. Recent work from our and others laboratory demonstrated that human RBCs carry an active type 3, endothelial NO synthase (eNOS), constitutively producing NO under normoxic conditions, the activity of which is compromised in patients with coronary artery disease. In this review we aim to discuss the potential role of red cell eNOS in RBC signaling and function, and to critically revise evidence to this date showing a role of non-endothelial circulating eNOS in cardiovascular pathophysiology.
Cardiovascular Research Laboratory, Department of Cardiology, Pneumology and Angiology, Medical Faculty, Heinrich Heine University of Düsseldorf, Düsseldorf, Germany.
Miriam M
MM
Cortese-Krott
Cardiovascular Research Laboratory, Department of Cardiology, Pneumology and Angiology, Medical Faculty, Heinrich Heine University of Düsseldorf, Düsseldorf, Germany.
Malte
M
Kelm
D000818:Animals; D001793:Blood Preservation; D002318:Cardiovascular Diseases / Q000097:blood / Q000201:enzymology* / Q000503:physiopathology; D042783:Endothelial Cells / Q000201:enzymology; D004905:Erythrocyte Aging; D004912:Erythrocytes / Q000201:enzymology*; D006439:Hemodynamics; D006706:Homeostasis; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000096:biosynthesis / Q000097:blood; D052250:Nitric Oxide Synthase Type III / Q000097:blood / Q000172:deficiency / Q000502:physiology*; D015398:Signal Transduction; D065227:Transfusion Reaction; D014664:Vasodilation / Q000502:physiology
D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse
Cardiovascular disease; Nitric oxide; Red blood cells; eNOS