Receptor for AGE (RAGE) Mediates Neointimal Formation in Response to Arterial Injury

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

doi:10.1161/01.cir.0000063577.32819.23

Cited by 169 publications

(181 citation statements)

References 28 publications

(24 reference statements)

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“…Compared with vehicle treatment (albumin), sRAGE-treated rats displayed a significant decrease in neointimal expansion. 49 A key finding in this study was the marked reduction in incorporation of bromodeoxyuridine in the smooth muscle cells of the expanding neointima in sRAGE-treated rats. These experiments strongly suggested that RAGE-expressing smooth muscle cells, at least in part, contributed importantly to diabetes-associated enhanced neointimal expansion after acute injury.…”

Section: Studies In Ratsmentioning

confidence: 64%

RAGE Axis

Naka

Bucciarelli

Wendt

et al. 2004

ATVB

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124

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Abstract-Receptor for AGE (RAGE) is a multi-ligand member of the immunoglobulin superfamily of cell surface molecules. Engagement of RAGE by its signal transduction ligands evokes inflammatory cell infiltration and activation in the vessel wall. In diabetes, when fueled by oxidant stress, hyperglycemia, and superimposed stresses such as hyperlipidemia or acute balloon/endothelial denuding arterial injury, the ligand-RAGE axis amplifies vascular stress and accelerates atherosclerosis and neointimal expansion. In this brief synopsis, we review the use of rodent models to test these concepts. Taken together, our findings support the premise that RAGE is an amplification step in vascular inflammation and acceleration of atherosclerosis. Future studies must rigorously test the potential impact of RAGE blockade in human subjects; such trials are on the horizon.

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Section: Studies In Ratsmentioning

confidence: 64%

RAGE Axis

Naka

Bucciarelli

Wendt

et al. 2004

ATVB

Self Cite

124

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“…In agreement with the cell culture studies, these data also suggest that hyperglycemia does not invoke unique mitogenic pathway but merely exaggerates the effects of other growth factors and cytokines. Thus, agents that prevent SMC growth in normal glucose, peroxisome proliferatoractivated receptor ␥ agonists (20), receptor for advanced glycation end products (41), and aldose reductase inhibitors (this study), also prevent high-glucose-induced SMC growth and arterial lesion formation.…”

Section: Discussionmentioning

confidence: 84%

Contribution of Aldose Reductase to Diabetic Hyperproliferation of Vascular Smooth Muscle Cells

et al. 2006

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“…Recent studies have implied the role of PPARγ in regulating vascular smooth muscle cell (VSMC) proliferation and migration, an essential event in the development of diabetic atherosclerosis 15, 16. Under diabetic conditions, the accumulation of hyperglycaemia‐induced AGEs and activation of the receptor for AGEs (RAGE) are key factors mediating these events 17, 18, 19. The objective of this study was to investigate stereo‐selective binding of Rg3 enantiomers to PPARγ based on the stereochemical structures and to explore whether differential PPARγ activation by Rg3 stereoisomers could lead to differential effects on AGEs‐stimulated proliferation and migration of VSMCs and diabetic atherosclerosis formation.…”

Section: Introductionmentioning

confidence: 99%

Ginsenoside Rg3 stereoisomers differentially inhibit vascular smooth muscle cell proliferation and migration in diabetic atherosclerosis

Guo

Xiao

et al. 2018

J Cellular Molecular Medi

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Ginsenoside 20(R/S)‐Rg3, as a natural peroxisome proliferator‐activated receptor gamma (PPARγ) ligand, has been reported to exhibit differential biological effects. It is of great interest to understand the stereochemical selectivity of 20(R/S)‐Rg3 and explore whether differential PPARγ activation by Rg3 stereoisomers, if it exists, could lead to differential physiological outcome and therapeutic effects in diabetic atherosclerosis. Here, we investigated the binding modes of 20(R/S)‐Rg3 stereoisomers in the PPARγ ligand‐binding domain (PPARγ‐LBD) using molecular modelling and their effects on smooth muscle cell proliferation and migration induced by advanced glycation end products (AGEs). The results revealed that 20(S)‐Rg3 exhibited stronger antiproliferative and antimigratory effects due to stronger PPARγ activation. To validate the in vitro results, we used a mice model with diabetic atherosclerosis and obtained that 20(S)‐Rg3 markedly reduced the plaque size secondary to reducing the proliferation and migration of VSMCs, while the plaques were more stable due to improvements in other plaque compositions. The results shed light on the structural difference between Rg3 stereoisomers that can lead to significant differential physiological outcome, and the (S)‐isomer seems to be the more potent isomer to be developed as a promising drug for diabetic atherosclerosis.

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Receptor for AGE (RAGE) Mediates Neointimal Formation in Response to Arterial Injury

Cited by 169 publications

References 28 publications

RAGE Axis

RAGE Axis

Contribution of Aldose Reductase to Diabetic Hyperproliferation of Vascular Smooth Muscle Cells

Ginsenoside Rg3 stereoisomers differentially inhibit vascular smooth muscle cell proliferation and migration in diabetic atherosclerosis

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