The study, published on Cell & Bioscience, includes two experimental approaches, one with mice and the other one with cell cultures.
This discovery may be the basis for the development of better treatments for this disease and means a paradigm shift
A study published on the journal Cell & Bioscience by the BIOHEART Cardiovascular Diseases Research Group of the Bellvitge Biomedical Research Institute (IDIBELL) reinforces the hypothesis that iron deficiency may play a key role in the progression of heart failure.
Bio-Heart is a multidisciplinary cardiovascular diseases research group led by Dr. Josep Comín, head of the Cardiology Service at Bellvitge University Hospital. The group consists of cardiologists, advanced practice nurses, biologists, internists, primary care physicians, and other related specialists who work together for a truly translational research, in order to introduce substantial changes into the medical practice.
Heart failure is the latest manifestation of the majority of heart diseases, and it occurs when the heart is unable to pump enough blood. This disease has a high prevalence (similar to that of some types of cancer) and is associated with high mortality, hospitalization, health care costs and a high impact on patients’ quality of life. The causes of heart failure are not yet well known at cell level. One of the most accepted theories suggests that it is promoted by an initial damage to the heart causing changes in its shape and function. In an attempt to restore heart function, a systemic response triggers the activation of both the nervous system and the hormonal system renin-angiotensin-aldosterone, inducing what is known as neurohormonal activation. Neurohormonal systems help maintain blood circulation stability.
In fact, the inhibition of this neurohormonal activation is the basis of modern pharmacological treatment for heart failure. However, these therapies have failed to promote a complete remission of symptoms and restore patient’s life expectancy from before their disease.
This has motivated an increasing interest in emerging therapeutic targets, which could deliver better results. Iron appears to be a good candidate as a new therapeutic target, since iron deficiency is present in up to 50% of heart failure patients and is associated with a worse evolution of the disease. Moreover, it is also well known that, apart from its role in oxygen transport, iron also plays an important role in the metabolism of cells with high demand for energy, such as heart cells. In order to gain a better understanding of the relationship between iron and heart failure, IDIBELL researchers designed a two-step experimental approach: one with mice and one with cell cultures. First, heart failure was induced in mice by using the drug isoproterenol and then their hearts were studied with analysis techniques such as PCR and immunoblotting.
The results showed a decrease in both iron levels and several iron regulatory molecules. Second, a commercial line of heart-derived cells was challenged with the typical heart-failure neurohormonal activation. Equally, the results showed both a depletion of intracellular iron levels and a decrease of iron regulatory molecules. Finally, the study also noticed that neurohormonal activation impaired the function of mitochondria (notice that these organelles, which work as power stations for the cells, require iron for their proper functioning). This research confirms, as other studies have previously suggested, the prominent role that mitochondria play in the progression of heart failure.
This finding, which calls for further in-depth research, helps to understand the positive effects of intravenous iron treatments already being given to some patients, and may be the basis for the development of better treatments for heart failure.
This new publication belongs to one of the strategic lines of research of Bio-Heart Cardiovascular Diseases Research Group. The leader of this group, Dr. Josep Comín, has pioneered the study of the clinical and pathophysiological role of iron metabolism abnormalities in heart failure. His studies have meant a paradigm shift placing iron deficiency not as an additional external complication of heart failure but as one of its causes at cellular level.