The red blood cell and vascular function in health and disease

Nitric oxide (NO) is widely accepted as a central regulator of vascular tone and a vast array of other cardiovascular signaling mechanisms. An emerging player in these mechanisms is hemoglobin (Hb), an erythrocytic protein that serves as the archetypical model for an allosteric protein. Specifically, red blood cells (RBC) are suggested to be integral in matching blood flow to tissue oxygen demands. The mechanisms proposed involve the ability of Hb to sense changes in oxygen concentrations and coupling this process to modulating vascular NO levels. The molecular basis of these mechanisms remains under investigation, but is clearly diverse and discussed in this article from the basis of the blood flow responses to hypoxia. Another emerging theme in RBC biology is the role of these cells during inflammatory disease in which disease processes promote the interaction of vascular NO and the RBC. This is exemplified in hemolytic diseases, in which released Hb has drastic affects on vascular homeostasis mechanisms. Additionally, it is becoming evident that RBC express numerous molecules that mediate interactions with the extracellular matrix and cellular mediators of inflammation. The functional implications for such interactions remain unclear but highlight potential roles of the RBC in modulating inflammatory disease.