Published online before print February 27, 2006, doi: 10.1161/CIRCULATIONAHA.105.575993
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2006;113:1226-1234.)
© 2006 American Heart Association, Inc.
Molecular Cardiology |
Receptor for Advanced-Glycation End Products
Key Modulator of Myocardial Ischemic Injury
From the Division of Surgical Science, Department of Surgery, Columbia University Medical Center, New York, NY.
Correspondence to Dr Ravichandran Ramasamy, Department of Surgery, Columbia University Medical Center, 630 W 168 St, Black Building 1706, New York, NY 10032. E-mail rr260{at}columbia.edu
Received July 14, 2005; revision received December 19, 2005; accepted December 23, 2005.
Background— The beneficial effects of reperfusion therapies have been limited by the amount of ischemic damage that occurs before reperfusion. To enable development of interventions to reduce cell injury, our research has focused on understanding mechanisms involved in cardiac cell death after ischemia/reperfusion (I/R) injury. In this context, our laboratory has been investigating the role of the receptor for advanced-glycation end products (RAGE) in myocardial I/R injury.
Methods and Results— In this study we tested the hypothesis that RAGE is a key modulator of I/R injury in the myocardium. In ischemic rat hearts, expression of RAGE and its ligands was significantly enhanced. Pretreatment of rats with sRAGE, a decoy soluble part of RAGE receptor, reduced ischemic injury and improved functional recovery of myocardium. To specifically dissect the impact of RAGE, hearts from homozygous RAGE-null mice were isolated, perfused, and subjected to I/R. RAGE-null mice were strikingly protected from the adverse impact of I/R injury in the heart, as indicated by decreased release of LDH, improved functional recovery, and increased adenosine triphosphate (ATP). In rats and mice, activation of the RAGE axis was associated with increases in inducible nitric oxide synthase expression and levels of nitric oxide, cyclic guanosine monophosphate (cGMP), and nitrotyrosine.
Conclusions— These findings demonstrate novel and key roles for RAGE in I/R injury in the heart. The findings also demonstrate that the interaction of RAGE with advanced-glycation end products affects myocardial energy metabolism and function during I/R.
CLINICAL PERSPECTIVE
This article has been cited by other articles:
 |
|
 |
|
  L. G. Bucciarelli, R. Ananthakrishnan, Y. C. Hwang, M. Kaneko, F. Song, D. R. Sell, C. Strauch, V. M. Monnier, S. F. Yan, A. M. Schmidt, et al. RAGE and Modulation of Ischemic Injury in the Diabetic Myocardium Diabetes, July 1, 2008; 57(7): 1941 - 1951. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Ramasamy, S. F. Yan, and A. M. Schmidt Stopping the Primal RAGE Reaction in Myocardial Infarction: Capturing Adaptive Responses to Heal the Heart? Circulation, June 24, 2008; 117(25): 3165 - 3167. [Full Text] [PDF]
|
|
|
|
|
|
M. Andrassy, H. C. Volz, J. C. Igwe, B. Funke, S. N. Eichberger, Z. Kaya, S. Buss, F. Autschbach, S. T. Pleger, I. K. Lukic, et al. High-Mobility Group Box-1 in Ischemia-Reperfusion Injury of the Heart Circulation, June 24, 2008; 117(25): 3216 - 3226. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Z. Feuerstein Cardiac RAGE in Sepsis: Call TOLL Free for Anti-RAGE Circ. Res., May 23, 2008; 102(10): 1153 - 1154. [Full Text] [PDF]
|
|
|
|
|
|
J. H. Boyd, B. Kan, H. Roberts, Y. Wang, and K. R. Walley S100A8 and S100A9 Mediate Endotoxin-Induced Cardiomyocyte Dysfunction via the Receptor for Advanced Glycation End Products Circ. Res., May 23, 2008; 102(10): 1239 - 1246. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. C. Burckhardt, D. Gozal, E. Dayyat, Y. Cheng, R. C. Li, A. D. Goldbart, and B. W. Row Green Tea Catechin Polyphenols Attenuate Behavioral and Oxidative Responses to Intermittent Hypoxia Am. J. Respir. Crit. Care Med., May 15, 2008; 177(10): 1135 - 1141. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Yamoah, A. Brebene, R. Baliram, K. Inagaki, G. Dolios, A. Arabi, R. Majeed, H. Amano, R. Wang, R. Yanagisawa, et al. High-Mobility Group Box Proteins Modulate Tumor Necrosis Factor-{alpha} Expression in Osteoclastogenesis via a Novel Deoxyribonucleic Acid Sequence Mol. Endocrinol., May 1, 2008; 22(5): 1141 - 1153. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Chang, T. Wendt, W. Qu, L. Kong, Y. S. Zou, A. M. Schmidt, and S.-F. Yan Oxygen Deprivation Triggers Upregulation of Early Growth Response-1 by the Receptor for Advanced Glycation End Products Circ. Res., April 25, 2008; 102(8): 905 - 913. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. D. Abel, S. E. Litwin, and G. Sweeney Cardiac Remodeling in Obesity Physiol Rev, April 1, 2008; 88(2): 389 - 419. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Aleshin, R. Ananthakrishnan, Q. Li, R. Rosario, Y. Lu, W. Qu, F. Song, S. Bakr, M. Szabolcs, V. D'Agati, et al. RAGE modulates myocardial injury consequent to LAD infarction via impact on JNK and STAT signaling in a murine model Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1823 - H1832. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Pichiule, J. C. Chavez, A. M. Schmidt, and S. J. Vannucci Hypoxia-inducible Factor-1 Mediates Neuronal Expression of the Receptor for Advanced Glycation End Products following Hypoxia/Ischemia J. Biol. Chem., December 14, 2007; 282(50): 36330 - 36340. [Abstract] [Full Text] [PDF]
|
|