Pathological Roles of Iron in Cardiovascular Disease

Iron is an essential mineral required for a variety of vital biological functions. Despite being vital for life, iron also has potentially toxic aspects. Iron has been investigated as a risk factor for coronary artery disease (CAD), however, iron's toxicity in CAD patients still remains controversial. One possible mechanism behind the toxicity of iron is "ferroptosis", a newly described form of irondependent cell death. Ferroptosis is an iron-dependent form of regulated cell death that is distinct from apoptosis, necroptosis, and other types of cell death. Ferroptosis has been reported in ischemiareperfusion (I/R) injury and several other diseases. Recently, we reported that ferroptosis is a significant form of cell death in cardiomyocytes. Moreover, myocardial hemorrhage, a major event in the pathogenesis of heart failure, could trigger the release of free iron into cardiac muscle and is an independent predictor of adverse left ventricular remodeling after myocardial infarction. Iron deposition in the heart can now be detected with advanced imaging methods, such as T2 star (T2*) cardiac magnetic resonance imaging, which can non-invasively predict iron levels in the myocardium and detect myocardial hemorrhage, thus existing technology could be used to assess myocardial iron. We will discuss the role of iron in cardiovascular diseases and especially with regard to myocardial I/R injury.