Their research suggests that an inability of red blood cells to relax blood vessels through the release of nitric oxide is a major factor behind the disease's primary symptoms -- including oxygen deprivation and blocked vessels that can lead to pain, clots and stroke. Thus, therapies that restore nitric oxide to blood cells might serve as a useful method for treating the disease, said HHMI researcher Jonathan Stamler, M.D., professor of pulmonary medicine and cardiology at Duke University Medical Center.
The researchers reported their findings on Jan. 31, 2005, in an early edition of Proceedings of the National Academy of Sciences.
The symptoms of sickle cell disease have generally been attributed to the physical obstruction of blood vessels by distorted, or "sickled," and rigid red cells, Stamler said. The new findings, for the first time, implicate abnormal vessel dilation by the red cells themselves in oxygen deficiency. That oxygen deficiency, in turn, may result in sickling and, ultimately, the irreversible obstruction of blood vessels.
Relieving the vascular constriction and resulting oxygen deficiency through the restoration of nitric oxide to red cell membranes might therefore prevent the disease symptoms, opening up a new realm of therapeutic possibilities, Stamler said. Current therapies fail to treat the disease itself and are instead geared toward minimizing pain and preventing infection, he added. In patients who become anemic, blood transfusions replenish the red blood cell supply in the body.
The team further found that differences among patients in their ability to
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Contact: Kendall Morgan
kendall.morgan@duke.edu
919-684-4148
Duke University Medical Center
31-Jan-2005