Iron deficiency is the single most common nutritional disorder worldwide and the main cause of anaemia in infancy, childhood, and pregnancy. It is prevalent in most of the developing world and it is probably the only nutritional deficiency of consideration in industrialized countries. In the developing world, the prevalence of iron deficiency is high and is due mainly to a low intake of bioavailable iron.
The prevalence of iron deficiency is particularly high in patients with cardiovascular diseases, in whom it is associated with poor outcomes.
Enlightening this, a new discovery by the Lakhal-Littleton Group at Oxford’s Department of Physiology Anatomy & Genetics suggests the way iron deficiency affects the vasculature of the lung.
Moreover, it is expected to hold the key to improving the treatment of pulmonary arterial hypertension.
It has been known for some time that iron deficiency predisposes to pulmonary arterial hypertension (PAH). In this condition, the vasculature in the lungs is constricted and remodeled, and this puts pressure on the right side of the heart. For some time, it was thought that PAH is caused by anaemia, a condition in which iron deficiency is the underlying mechanism. Consequently, the only consideration given to iron deficiency in the clinical setting has been in the context of correcting anaemia.
Prior study has suggested that iron deficiency within tissues, such as the heart, is sufficient to cause disease even in the absence of anaemia. In this new study, scientists explored the link between iron deficiency and PAH. It has been found that iron deficiency within the smooth muscle cells of the pulmonary arteries is in itself sufficient to cause PAH, even in the absence of anaemia. The effect of iron deficiency is due to the increased release of the vasoconstrictor endothelin-1 from cells of the pulmonary arteries.
Scientists were able to reverse and prevent PAH in mice by both iron supplementation and inhibition of endothelin-1 signaling. Consequently, this study provides a mechanistic underpinning for the observation that iron deficiency raises hypoxic pulmonary arterial pressure in healthy individuals and worsens existing PAH in patients.
In other words, the study demonstrates that it is not anaemia, but rather the lack of iron in the cells of the vasculature that is causing the remodeling of the vessels in the lung present in individuals suffering from PAH. Thus, it reinforces the rationale for the correction of tissue iron deficiency independently of the presence or absence of anaemia.
Associate Professor Samira Lakhal-Littleton said, ‘This research holds the potential to alter the way in which patients with pulmonary arterial hypertension are treated.
‘This provides the rationale for giving iron to patients even when they aren’t anaemic, because the target is no longer anaemia, but iron deficiency within tissues.’