Cardiologia Clínica e Experimental
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Design and Rationale for the Study of Changes in Iron and Atherosclerosis Risk in Perimenopause

Georgeta Mihai, Xin He, Xiaolan Zhang, Beth McCarthy, Tam Tran, Michael Pennell, Jessica Blank, Orlando P. Simonetti, Rebecca D. Jackson and Subha V. Raman

This study seeks to investigate changes in iron homeostasis and carotid arteries in women at risk of atherosclerosis, addressing a relatively unexplored hypothesis explaining why women have a 5-10 year lag in initial atherosclerotic events. Recent evidence points to hepcidin, the key regulator of macrophage iron uptake and release, as a potential mediator of risk. Furthermore, iron catalyzes the generation of free radicals that oxidize cholesterol stimulating atheroma formation. Magnetic resonance imaging (MRI) is ideally suited to study iron because of iron's local effects on magnetic susceptibility that can be quantified using a relaxation parameter called T2* ('T2-star'), as well as the ability to noninvasively characterize and quantify atherosclerotic plaque with MRI. This work outlines the rationale and study design to provide critical evidence related to the iron hypothesis, such that novel diagnostics and therapeutics to attenuate risk may be derived from a better understanding of iron's role in atherosclerosis.