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(Circulation Research. 2008;102:6.)
© 2008 American Heart Association, Inc.

Editorials

Heme–Egr-1

New Partners in Atherosclerotic Progression?

Gregg Rokosh

From the Institute of Molecular Cardiology, University of Louisville, Ky.

Correspondence to Gregg Rokosh, 570 South Preston St, University of Louisville, Louisville, KY 40202. E-mail gregg.rokosh@louisville.edu

See related article, pages 42–50

Key Words: heme • early growth response-1 • atherosclerosis

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

Heme, Fe-protoporphyrin IX, is an essential building block for oxygen carrying hemoglobin and myoglobin. Physiologic recycling of heme occurs in many tissues, predominantly in the reticuloendothelial system, and is dependent on hemoxygenase-1 (HO-1). Heme is degraded by HO-1 into constituent carbon monoxide (CO), Fe²⁺, and biliverdin and then converted to bilirubin. CO and biliverdin possess beneficial attributes through signaling and antioxidative capacities, respectively, whereas Fe²⁺ is a strong oxidant. The oxidative capacity of Fe²⁺ is contained by ferritin, a Fe²⁺-binding protein that serves as a chaperone transporting Fe²⁺ for synthesis of iron containing proteins. The importance of heme metabolism has been highlighted in clinical observations in which the lack of capacity to degrade heme observed in a 6-year-old child with HO-1 deficiency was associated with plaque formation in the aorta and hyperlipidemia,¹ and low HO-1 expression is correlated with increased cardiovascular risk. These findings are strongly supported by studies in mice lacking HO-1.² Thus it is clear that lack of HO-1 is detrimental in the cardiovascular system; however, one must consider whether the increased risk is attributable to the accumulation of heme or the consequences of decreased heme degradation products?

Changes in vascular homeostasis with disease or injury inevitably lead to increased oxidative stress. This in part is a consequence of elevated local and circulating heme. Unbound heme, is a strong oxidant, and its hydrophobic nature permits rapid entry into cells of the vascular wall. Once heme enters the lipid bilayer within the cell, it is readily capable . . . [Full Text of this Article]

Related Article:

Hemin Upregulates Egr-1 Expression in Vascular Smooth Muscle Cells via Reactive Oxygen Species ERK-1/2–Elk-1 and NF-B

Rukhsana N. Hasan and Andrew I. Schafer
Circ. Res. 2008 102: 42-50. [Abstract] [Full Text] [PDF]