Receptor for AGE (RAGE) mediates neointimal formation in response to arterial injury

Zhongmin Zhou, Kai Wang, Marc S. Penn, Steven P. Marso, Michael A. Lauer, Farhad Forudi, Xiaorong Zhou, Wu Qu, Yan Lu, David M. Stern, Ann Marie Schmidt, A. Michael Lincoff, Eric J. Topol

Research output: Contribution to journalArticle

146 Scopus citations

Abstract

Background - Receptor for advanced-glycation end products (RAGE) and its ligands AGEs and S100/calgranulins have been implicated in a range of disorders. However, the role of RAGE/ligand interaction in neointimal hyperplasia after vascular injury remains unclear. Methods and Results - We examined the expression of RAGE and its ligands after balloon injury of the carotid artery in both Zucker diabetic and nondiabetic rats. Using a soluble portion of the extracellular domain of RAGE, we determined the effects of suppressing RAGE/ligand interaction on vascular smooth muscle cell (VSMC) proliferation and neointimal formation after arterial injury. We demonstrate a significantly increased accumulation of AGE and immunoreactivities of RAGE and S100/calgranulins in response to balloon injury in diabetic compared with nondiabetic rats. Blockade of RAGE/ligand interaction significantly decreased S100-stimulated VSMC proliferation in vitro and bromodeoxyuridine (BrdU)-labeled proliferating VSMC in vivo, and suppressed neointimal formation and increased luminal area in both Zucker diabetic and nondiabetic rats. Conclusions - These findings indicate that RAGE/ligand interaction plays a key role in neointimal formation after vascular injury irrespective of diabetes status and suggest a novel target to minimize neointimal hyperplasia.

Original languageEnglish (US)
Pages (from-to)2238-2243
Number of pages6
JournalCirculation
Volume107
Issue number17
DOIs
Publication statusPublished - May 6 2003

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Keywords

  • Angioplasty
  • Diabetes mellitus
  • Receptors
  • Restenosis

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Zhou, Z., Wang, K., Penn, M. S., Marso, S. P., Lauer, M. A., Forudi, F., ... Topol, E. J. (2003). Receptor for AGE (RAGE) mediates neointimal formation in response to arterial injury. Circulation, 107(17), 2238-2243. https://doi.org/10.1161/01.CIR.0000063577.32819.23