Iron, Atherosclerosis, and Neurodegeneration: A Key Role for Cholesterol in Promoting Iron‐Dependent Oxidative Damage?

Abstract

This article reviews the roles and interactions of iron, atherosclerosis, and neurodegeneration. It highlights the importance of cholesterol in promoting iron-dependent oxidative damage. An intriguing possibility is that hypercholesterolemia can increase brain iron load and both the aggregation of beta-amyloid and the ability of iron on plaques to catalyze oxidative damage. This could explain why hypercholesterolemia is a risk factor for Alzheimer's disease. Further work is necessary to study the mechanism of increased iron transport across the blood brain barrier in atherosclerosis.

High-resolution ultrahigh-field MRI of stroke

“…Iron deposits have been associated with Alzheimer's disease, Parkinson's disease, multiinfarct dementia and adverse outcome after strokes [1]. Visualization of microvessels and tissue iron deposits can be helpful for the diagnosis of small-vessel atherosclerosis [18]. Quantification of tissue iron may serve as a marker of small-vessel disease, indicating an increased permeability of the blood-brain barrier with small-vessel disease and after a stroke.…”

Lipid homeostasis and apolipoprotein E in the development and progression of Alzheimer's disease

“…Increased serum cholesterol could result in increased endocytic transfer of serum transferrin-bound iron into endothelial cells and therefore increased transport of iron across the BBB (100). In the brain, iron is concentrated predominantly in glial cells, and increased iron staining in oligodendrocytes is seen in the brains of rabbits fed high-cholesterol diets (100). This increase in iron may further increase the vulnerability of the brain to oxidative stress.…”

Melatonin Prevents Myeloperoxidase Heme Destruction and the Generation of Free Iron Mediated by Self-Generated Hypochlorous Acid

“…The association between enhanced MPO expression and increased levels of free iron is characteristic of many inflammatory disorders including cardiovascular diseases such atherosclerosis, pulmonary diseases such as cystic fibrosis, neurodegenerative diseases such as Alzheimer's disease as well as arthritis, diabetes, and has been found to be a risk factor for various cancers [28,29,31,[70][71][72][73][74][75]. As free iron accumulates, it disturbs body processes by replacing certain vital minerals such as zinc, copper, and manganese in many enzymes, depleting vitamins such as vitamin E and D, and may lead to chronic infection and inflammation [76].…”

“…However, under a number of pathological conditions such as inflammatory diseases, in which ROS production can become excessive, HOCl is capable of mediating tissue damage [19,27]. Interestingly, many inflammatory disorders such as ovarian cancer and atherosclerosis, in which MPO/HOCl have been known to be elevated, are also associated with significant free iron accumulation [28][29][30][31]. Recently, we have highlighted the potential link between elevated HOCl and hemoprotein heme destruction, and subsequent generation of free iron [21,32,33].…”