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 Stern, Ann Marie Schmidt, A. Michael Lincoff, Eric J. Topol

Research output: Contribution to journalArticle

145 Citations (Scopus)

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
StatePublished - May 6 2003
Externally publishedYes

Fingerprint

Wounds and Injuries
Ligands
Vascular Smooth Muscle
Leukocyte L1 Antigen Complex
Smooth Muscle Myocytes
Vascular System Injuries
Hyperplasia
Cell Proliferation
Carotid Artery Injuries
Advanced Glycosylation End Product-Specific Receptor
Bromodeoxyuridine

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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

Receptor for AGE (RAGE) mediates neointimal formation in response to arterial injury. / Zhou, Zhongmin; Wang, Kai; Penn, Marc S.; Marso, Steven P.; Lauer, Michael A.; Forudi, Farhad; Zhou, Xiaorong; Qu, Wu; Lu, Yan; Stern, David; Schmidt, Ann Marie; Lincoff, A. Michael; Topol, Eric J.

In: Circulation, Vol. 107, No. 17, 06.05.2003, p. 2238-2243.

Research output: Contribution to journalArticle

Zhou, Z, Wang, K, Penn, MS, Marso, SP, Lauer, MA, Forudi, F, Zhou, X, Qu, W, Lu, Y, Stern, D, Schmidt, AM, Lincoff, AM & Topol, EJ 2003, 'Receptor for AGE (RAGE) mediates neointimal formation in response to arterial injury', Circulation, vol. 107, no. 17, pp. 2238-2243. https://doi.org/10.1161/01.CIR.0000063577.32819.23
Zhou, Zhongmin ; Wang, Kai ; Penn, Marc S. ; Marso, Steven P. ; Lauer, Michael A. ; Forudi, Farhad ; Zhou, Xiaorong ; Qu, Wu ; Lu, Yan ; Stern, David ; Schmidt, Ann Marie ; Lincoff, A. Michael ; Topol, Eric J. / Receptor for AGE (RAGE) mediates neointimal formation in response to arterial injury. In: Circulation. 2003 ; Vol. 107, No. 17. pp. 2238-2243.
@article{d9a857d4b091428f86816dd2ccf6a3d1,
title = "Receptor for AGE (RAGE) mediates neointimal formation in response to arterial injury",
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.",
author = "Zhongmin Zhou and Kai Wang and Penn, {Marc S.} and Marso, {Steven P.} and Lauer, {Michael A.} and Farhad Forudi and Xiaorong Zhou and Wu Qu and Yan Lu and David Stern and Schmidt, {Ann Marie} and Lincoff, {A. Michael} and Topol, {Eric J.}",
year = "2003",
month = "5",
day = "6",
doi = "10.1161/01.CIR.0000063577.32819.23",
language = "English (US)",
volume = "107",
pages = "2238--2243",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "17",

}

TY - JOUR

T1 - Receptor for AGE (RAGE) mediates neointimal formation in response to arterial injury

AU - Zhou, Zhongmin

AU - Wang, Kai

AU - Penn, Marc S.

AU - Marso, Steven P.

AU - Lauer, Michael A.

AU - Forudi, Farhad

AU - Zhou, Xiaorong

AU - Qu, Wu

AU - Lu, Yan

AU - Stern, David

AU - Schmidt, Ann Marie

AU - Lincoff, A. Michael

AU - Topol, Eric J.

PY - 2003/5/6

Y1 - 2003/5/6

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0037696629&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037696629&partnerID=8YFLogxK

U2 - 10.1161/01.CIR.0000063577.32819.23

DO - 10.1161/01.CIR.0000063577.32819.23

M3 - Article

VL - 107

SP - 2238

EP - 2243

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 17

ER -