Low levels of both oxygen and the powerful blood vessel dilator nitric oxide appear to have an unfortunate synergy for patients with sickle cell disease, researchers report.
Their studies indicate that the two conditions common in sickle cell disease, dramatically increase red blood cells' adhesion to the lining of blood vessels walls and the debilitating pain crises that can result.
The good news is that restoring normal levels of nitric oxide can substantially reduce red blood cell adhesion, said Dr. Tohru Ikuta, a molecular hematologist at the Medical College of Georgia at Georgia Regents University. Ikuta and Dr. C. Alvin Head, former Chairman of MCG's Department of Anesthesiology and Perioperative Medicine, are co-corresponding authors of the study in the journal Blood.
The study also points to a potentially new therapeutic target, the self-adhesion molecule P-selectin, which the researchers found played a central role in increased red blood cell adhesion. Low levels of oxygen and nitric oxide both increase expression of P-selectin.
Hypoxia, or low oxygen levels, can strike anyone in the face of, for instance, the flu, a bad cold, strenuous exercise or exposure to high altitudes. Additionally, sickle cell patients can have chronic problems with oxygen delivery.
Oxygen is carried in hemoglobin, which travels the bloodstream to its target tissue inside typically flexible, oval-shaped red blood cells. The sickled shape of the hemoglobin in sickle cell disease can impede the journey and often results in oddly shaped, fragile red blood cells as well, said Ikuta. These red blood cells can spill their contents into the bloodstream, where oxygen readily binds with the nitric oxide and patients quickly find themselves with insufficient levels of both.
To understand the relationship between low levels of oxygen and nitric oxide, researchers infused sickled red blood cells into mice incapable of p
|Contact: Toni Baker|
Medical College of Georgia at Georgia Regents University