Iron overload, oxidative stress and vascular dysfunction: Evidences from clinical studies and animal models

• Published in: Biochimica et biophysica acta. General subjects 2022-09, Vol.1866 (9), p.130172-130172, Article 130172
• Main Authors: dos Santos, Leonardo, Bertoli, Sabrina Rodrigues, Ávila, Renata Andrade, Marques, Vinícius Bermond
• Format: Article
• Language: English
• Subjects: Atherosclerosis; Endothelial dysfunction; Hemochromatosis; iron hypothesis; Iron status; Oxidative stress
• ISSN: 0304-4165; 1872-8006
• DOI: 10.1016/j.bbagen.2022.130172

Although iron is a metal involved in many vital processes due to its redox capacity, body iron overloads lead to tissue damage, including the cardiovascular system. While cardiomyopathy was the focus since the 1960s, the impact on the vasculature was comparatively neglected for about 40 years, when clinical studies correlating iron overload, oxidative stress, endothelial dysfunction, arterial stiffness and atherosclerosis reinforced an “iron hypothesis”. Due to controversial results from some epidemiological studies investigating atherosclerotic events and iron levels, well-controlled trials and animal studies provided essential data about the influence of iron, per se, on the vasculature. As a result, the pathophysiology of vascular dysfunction in iron overload have been revisited. This review summarizes the knowledge obtained from epidemiological studies, animal models and “in vitro” cellular systems in recent decades, highlighting a more harmful than innocent role of iron excess for the vascular homeostasis, which supports our proposal to hereafter denominate “iron overload vasculopathy”. Additionally, evidence-based potential therapeutic targets are pointed out to be tested in pre-clinical research that may be useful in cardiovascular protection for patients with iron overload syndromes. •Despite the consensual iron overload cardiomyopathy, the vessels still under debate.•Well-controlled clinical/animal studies in the last 2 decades have been decisive.•Strong evidences indicate iron-induced structural and functional vascular changes.•The vascular oxidative stress mediate endothelial dysfunction and atherosclerosis.•However, there are still gaps and therapeutic targets to reduce cardiovascular risk to be searched.