NIH-supported researchers recently discovered that in mice, lack of iron regulatory protein 1 (Irp1) results in pulmonary hypertension, a form of high blood pressure that affects the lungs, and to polycythemia, a rare disorder in which the body produces excess red blood cells. Iron regulatory protein 1 (Irp1) detects iron levels in cells and directs either the storage or use of iron, depending on other conditions in the body. The researchers found that mice lacking Irp1 produced high levels of hypoxia inducible factor 2-alpha (HIF2 alpha), a protein produced in response to low oxygen conditions, like those that occur at high altitudes. In turn, HIF2 alpha spurs production of the hormone erythropoietin, which stimulates the production of red blood cells.
To investigate Irp1’s role in regulating the body’s use of iron, researchers in the Section on Human Iron Metabolism, part of the Molecular Medicine Program in the Division of Intramural Research, reared mice lacking the gene that makes Irp1 and divided the animals into two groups, feeding one group a normal diet and the other a low iron diet. Within a year, less than 40% of the mice on the low-iron diet had survived. Most had died from abdominal hemorrhaging. The researchers found that the mice on low-iron diets had high levels of HIF2 alpha in the lungs and kidney. These animals produced high levels of erythropoietin, which resulted in polycythemia. HIF2 alpha also triggered increased production of a substance known as endothelin-1 in the lungs, which likely contributed to the development of pulmonary hypertension.
In people, polycythemia and high blood pressure in the lungs are rare conditions, and in some cases occur without a known cause. It is possible that changes in the gene for Irp1 may account for some of these cases, the researchers suggest (PMID: 23395173).