Researchers at U of T may have found a way to prevent heart failure and death in people who suffer from high levels of iron in their blood.
The only treatment currently available for this condition is expensive and painful. Scientists here however discovered that drugs currently being used to lower blood pressure, called anti-hypertensives, may be an easier and cheaper way to treat these patients.
People with diseases such as sickle cell anemia have unusually high levels of iron in their blood, which can lead to heart failure and death. Dr. Peter Backx, professor of Physiology and Medicine and an author of the article that appears in the journal Nature Medicine, explained how some diseases, like sickle cell anemia or thalassemia, cause iron overload. Red blood cells carry iron, but in these diseases the red blood cells are defective. People with sickle cell anemia for example have red blood cells shaped not like slightly flattened spheres, but like crescent moons (hence the name “sickle cell”). “This leads to increased iron absorption from the diet. People with sickle cell anemia and thalassemia also require blood transfusions on a regular basis, [and] transfusions are filled with iron [contained in the red blood cells].”
This excess iron enters the cells of the body through calcium channels, gates that allow calcium into cells. Calcium channels are “part of the body’s natural functioning,” according to Dr. Gavin Oudit, a cardiologist in the University Health Network and the lead author of the research paper. For example, in the heart, calcium channels let calcium into heart cells, which makes the heart contract. Iron can also enter human cells by way of these calcium channels. The human body requires small amounts of iron because this metal carries oxygen in the red blood cells, but too much iron can have detrimental effects. If too much iron enters cells via the calcium channels, the cells undergo stress and die. This is why high iron can lead to heart failure.
Anti-hypertensive drugs called calcium channel blockers prevent iron overload because they close calcium channels and therefore stop iron from entering cells. This is a big improvement when compared to the current treatment available, called chelation therapy. Chelation therapy only removes excess iron from the blood, but it cannot prevent iron from building up and causing tissue damage. Calcium channel blockers prevent iron from accumulating to dangerous levels inside cells. Dr. Peter Liu, professor of Physiology and Medicine and senior investigator of the study, pointed out “since the drugs being considered have already been approved for human use, the potential for clinical benefit could be realized much earlier than other treatment strategies.”
So far, the researchers have only examined the effects of calcium channel blockers on mice with iron-overload heart disease. As such, more trials have to be carried out on humans with sickle-cell anemia, thalassemia, and hereditary hemochromatosis. Given the proven safety of the anti-hypertensives tested, they could prevent early death from heart disease for many patients.
