Sickle cell anemia and vascular dysfunction: the nitric oxide connection.
Endothelial dysfunction and impaired nitric oxide bioavailability have been implicated in the pathogenesis of sickle cell anemia. Nitric oxide is a diatomic gas with a role in vascular homeostasis. Hemoglobin polymerization resulting from the HbS mutation produces erythrocyte deformation and hemolysis. Free hemoglobin, released into plasma by hemolysis scavenges on nitric oxide, and leads to reduced nitric oxide bioavailability. Pulmonary hypertension is a known consequence of sickle cell anemia. It occurs in 30-40% of patients with sickle cell anemia, and is associated with increased mortality. Several studies have implicated intravascular hemolysis, and impaired nitric oxide bioavailability in the pathogenesis of pulmonary hypertension. In this review, we summarize the mechanisms of altered nitric oxide bioavailability in sickle cell anemia and its possible role in the pathogenesis of pulmonary hypertension.
Akinsheye
Idowu
I
Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Klings
Elizabeth S
ES
D000755:Anemia, Sickle Cell / Q000235:genetics / Q000503:physiopathology*; D000818:Animals; D004730:Endothelium, Vascular / Q000503:physiopathology*; D020022:Genetic Predisposition to Disease; D006454:Hemoglobins / Q000378:metabolism; D006461:Hemolysis; D006801:Humans; D006976:Hypertension, Pulmonary / Q000503:physiopathology; D019255:NADPH Oxidases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress; D014969:Xanthine Oxidase / Q000378:metabolism
D006454:Hemoglobins; D016877:Oxidants; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D014969:Xanthine Oxidase; D019255:NADPH Oxidases