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BioTechnologia
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2/2011
vol. 92
 
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REVIEW PAPER
Do changes in iron metabolism contribute to the acceleration of the atherosclerosis process?

Dorota Formanowicz

BioTechnologia vol. 92(2) C pp. 180-192 C 2011
Online publish date: 2014/10/28
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There are several risk factors whose association with atherosclerosis, a chronic disease with complicated etiology,

is well established, including age, gender, smoking, lipids metabolism disorders, diabetes mellitus, obesity and reduced

physical activity. Surprisingly, many cardiovascular related deaths occur in individuals without standard

risk factors, so it has been suggested that these cases must be the result of other factors, previously not taken

into account. This phenomenon resulted in the development of research focused on finding new risk factors.

In 1981, Sullivan first postulated the so-called “iron hypothesis”, suggesting that the regular menstrual iron loss,

rather than other known effects of estrogen, protects women against coronary heart disease. It is widely believed

at present, that iron is an essential catalyst in the oxidation and oxidative modification of low-density lipoprotein

cholesterol which appears to be one of the pivotal steps in the early phase of the formation of the atherosclerotic

plaque. Thus, iron depletion through menstrual loss might reduce oxidative stress and beneficially affect atherogenesis.

Stored iron appears to be essential in the process of atherogenesis which is strictly required for normal

cellular metabolism but also serves as a reservoir from which toxic-active iron can be liberated under atherogenic

stimuli and result in lipid peroxidation. In this process, two pathways i.e., iron homeostasis metabolic pathway

and metabolic pathways involving proinflammatory cytokines are closely interconnected. In human monocytes,

these cytokines also increase the uptake of non-transferrin-bound iron, via the stimulation of divalent metal transporter-

1 synthesis and cause iron retention by down-regulating ferroportin synthesis. It has been found recently

that iron depositions are prominent in human atherosclerosis lesions. It can therefore be concluded that the

results of scientific research, particularly those of the last ten years, provide a strong pathological basis to support

the role of iron metabolism alterations in vascular damage and in the progression of atherosclerosis process.
keywords:

iron, atherosclerosis, inflammation, oxidative stress



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