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(Circulation. 2008;117:3165-3167.)
© 2008 American Heart Association, Inc.

Editorial

Stopping the Primal RAGE Reaction in Myocardial Infarction

Capturing Adaptive Responses to Heal the Heart?

Ravichandran Ramasamy, PhD; Shi Fang Yan, MD; Ann Marie Schmidt, MD

From the Division of Surgical Science, Department of Surgery, Columbia University Medical Center, New York, NY.

Correspondence to Dr Ann Marie Schmidt, Division of Surgical Science, Department of Surgery, Columbia University Medical Center, 630 W 168th St, P&S 17–401, New York, NY 10032. E-mail: ams11@columbia.edu

Key Words: Editorials • infarction • myocardium

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

	Introduction

 
The report of Andrassy and colleagues¹ in the current issue of Circulation adds to the growing body of evidence that the receptor for advanced glycation end products (RAGE) and its ligands, particularly high mobility group box-1 (HMGB1), are central mediators of ischemia/reperfusion (I/R) injury in the heart.^1–4 A major cause of injury, especially in the reperfusion phase, is the influx of inflammatory cells into the stressed heart. Andrassy and colleagues show that infiltrating leukocytes express proinflammatory HMGB1 and that HMGB1 plays fundamental roles in injury responses in the I/R heart. In homeostasis, HMGB1 is largely a nuclear protein. In stress conditions, HMGB1 may be released from injured cells, particularly on necrosis. The chief receptor for HMGB1, RAGE, is expressed in multiple cell types in the I/R heart, such as inflammatory cells, and also in cardiomyocytes and vascular cells (endothelial cells and smooth muscle cells).² Although HMGB1 may interact with distinct receptors beyond RAGE (for example, toll receptors),⁵ the current study of Andrassy and colleagues reveals major roles for RAGE in transducing the effects of HMGB1 in the heart, as administration of recombinant HMGB1 or antagonists of this molecule had significant proinjury effects in the wild-type mouse heart, but no additive effects were noted in mice devoid of RAGE. The biology of RAGE, however, is complex and extends beyond HMGB1 in the injured heart.

Article p 3216

	RAGE is a Multiligand Receptor: Impact on Myocardial Infarction

 
In addition to HMGB1, other ligands of RAGE likely play pivotal roles in the response to ischemia or I/R in the heart. For example, . . . [Full Text of this Article]

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