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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:2235.)
© 2005 American Heart Association, Inc.

Editorials

Iron Chelation and Vascular Function

In Search of the Mechanisms

Dardo E. Ferrara; W. Robert Taylor

From the Division of Cardiology (D.E.F., W.R.T.), Department of Medicine, Emory University School of Medicine, Atlanta, and Veterans Affairs Medical Center (W.R.T.), Atlanta, Ga.

Correspondence to W. Robert Taylor, MD, PhD, Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322. E-mail wtaylor@emory.edu

An extract of the first 250 words of the full text is provided, because this article has no abstract.

In 1981, Sullivan suggested that a state of iron depletion (ie, reduced iron stores without anemia) was potentially protective against coronary heart disease (CHD).¹ This original "iron hypothesis" was an attempt to explain the known sex difference in cardiovascular (CV) risk and the subsequent loss of the protective effect of female gender with menopause. This initial hypothesis was based in part on the observation that men exhibited an age-dependent increase in the accumulation of iron that was not seen in women until after menopause. This, coupled with the observation that hysterectomy without oophorectomy was associated with an increased CHD risk, supported the concept that a diminution in iron stores was protective against CHD. Basic and clinical data have recently begun to provide plausible explanations for a link between iron and atherosclerosis.^2,3

See page 2282

The toxic effect of free iron has been linked to oxidative stress through the Fenton reaction, where Fe²⁺ oxidizes H₂O₂ leading to its autooxidation and the generation of hydroxyl radicals⁴ which in turn initiate lipid peroxidation. In addition, biological forms of iron such as heme have the potential to catalyze other oxidative reactions. For example, heme can initiate the oxidation of isolated LDL in vitro⁴ and, in contrast to free transition metals, LDL in diluted serum.⁵ Iron is also essential for the synthesis of enzymes that can play a central role in vascular function and atherosclerosis (eg, eNOS, 5-lipoxygenase, and myeloperoxidase).

The amount of free ferrous (Fe²⁺) iron is normally maintained at a very . . . [Full Text of this Article]

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