Hemoglobin α in the blood vessel wall

• Published in: Free radical biology & medicine 2014-08, Vol.73, p.136-142
• Main Authors: Butcher, Joshua T., Johnson, Tyler, Beers, Jody, Columbus, Linda, Isakson, Brant E.
• Format: Article
• Language: English
• Subjects: Blood Pressure - physiology; Cytochrome b5 reductase 3; Endothelium, Vascular - physiology; Free radicals; Hemoglobin; Hemoglobin α; Hemoglobins - genetics; Hemoglobins - metabolism; Humans; Muscle, Smooth - blood supply; Muscle, Smooth - metabolism; Myoendothelial junction; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase Type III - metabolism; Peptide Fragments - genetics; Peptide Fragments - metabolism; Pulmonary Gas Exchange; Regional Blood Flow - physiology; Vascular Resistance - physiology; α-Thalassemia
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2014.04.019

Hemoglobin has been studied and well characterized in red blood cells for over 100 years. However, new work has indicated that the hemoglobin α subunit (Hbα) is also found within the blood vessel wall, where it appears to localize at the myoendothelial junction (MEJ) and plays a role in regulating nitric oxide (NO) signaling between endothelium and smooth muscle. This discovery has created a new paradigm for the control of endothelial nitric oxide synthase activity, nitric oxide diffusion, and, ultimately, vascular tone and blood pressure. This review discusses the current knowledge of hemoglobin׳s properties as a gas exchange molecule in the bloodstream and extrapolates the properties of Hbα biology to the MEJ signaling domain. Specifically, we propose that Hbα is present at the MEJ to regulate NO release and diffusion in a restricted physical space, which would have powerful implications for the regulation of blood flow in peripheral resistance arteries. [Display omitted] •The genetic background, vascular implications, and clinical phenotype of α-thalassemia are summarized.•The myoendothelial junction and the role that nitric oxide plays in vasculature are reviewed.•The oxidation state of the iron in hemoglobin α regulates nitric oxide diffusion.•The structure and function of hemoglobin α in the endothelium are described.•We discuss nature׳s deletion model of hemoglobin, the icefishes of the family Channichthyidae.