Central role of RAGE-dependent neointimal expansion in arterial restenosis

Taichi Sakaguchi, Shi Fang Yan, Shi Du Yan, Dmitri Belov, Ling Ling Rong, Monica Sousa, Martin Andrassy, Steven P. Marso, Stephan Duda, Bernd Arnold, Birgit Liliensiek, Peter P. Nawroth, David Stern, Ann Marie Schmidt, Yoshifumi Naka

Research output: Contribution to journalArticle

293 Citations (Scopus)

Abstract

Cellular proliferation, migration, and expression of extracellular matrix proteins and MMPs contribute to neointimal formation upon vascular injury. Wild-type mice undergoing arterial endothelial denudation displayed striking upregulation of receptor for advanced glycation end products (RAGE) in the injured vessel, particularly in activated smooth muscle cells of the expanding neointima. In parallel, two of RAGE's signal transducing ligands, advanced glycation end products (AGEs) and S100/calgranulins, demonstrated increased deposition/expression in the injured vessel wall. Blockade of RAGE, employing soluble truncated receptor or antibodies, or in homozygous RAGE null mice, resulted in significantly decreased neointimal expansion after arterial injury and decreased smooth muscle cell proliferation, migration, and expression of extracellular matrix proteins. A critical role for smooth muscle cell RAGE signaling was demonstrated in mice bearing a transgene encoding a RAGE cytosolic tail-deletion mutant, specifically in smooth muscle cells, driven by the SM22α promoter. Upon arterial injury, neointimal expansion was strikingly suppressed compared with that observed in wild-type littermates. Taken together, these data highlight key roles for RAGE in modulating smooth muscle cell properties after injury and suggest that RAGE is a logical target for suppression of untoward neointimal expansion consequent to arterial injury.

Original languageEnglish (US)
Pages (from-to)959-972
Number of pages14
JournalJournal of Clinical Investigation
Volume111
Issue number7
DOIs
StatePublished - Apr 1 2003

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Smooth Muscle Myocytes
Extracellular Matrix Proteins
Wounds and Injuries
Cell Proliferation
Leukocyte L1 Antigen Complex
Neointima
Advanced Glycosylation End Products
Vascular System Injuries
Matrix Metalloproteinases
Transgenes
Cell Movement
Advanced Glycosylation End Product-Specific Receptor
Tail
Up-Regulation
Ligands
Antibodies

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Sakaguchi, T., Yan, S. F., Yan, S. D., Belov, D., Rong, L. L., Sousa, M., ... Naka, Y. (2003). Central role of RAGE-dependent neointimal expansion in arterial restenosis. Journal of Clinical Investigation, 111(7), 959-972. https://doi.org/10.1172/JCI200317115

Central role of RAGE-dependent neointimal expansion in arterial restenosis. / Sakaguchi, Taichi; Yan, Shi Fang; Yan, Shi Du; Belov, Dmitri; Rong, Ling Ling; Sousa, Monica; Andrassy, Martin; Marso, Steven P.; Duda, Stephan; Arnold, Bernd; Liliensiek, Birgit; Nawroth, Peter P.; Stern, David; Schmidt, Ann Marie; Naka, Yoshifumi.

In: Journal of Clinical Investigation, Vol. 111, No. 7, 01.04.2003, p. 959-972.

Research output: Contribution to journalArticle

Sakaguchi, T, Yan, SF, Yan, SD, Belov, D, Rong, LL, Sousa, M, Andrassy, M, Marso, SP, Duda, S, Arnold, B, Liliensiek, B, Nawroth, PP, Stern, D, Schmidt, AM & Naka, Y 2003, 'Central role of RAGE-dependent neointimal expansion in arterial restenosis', Journal of Clinical Investigation, vol. 111, no. 7, pp. 959-972. https://doi.org/10.1172/JCI200317115
Sakaguchi, Taichi ; Yan, Shi Fang ; Yan, Shi Du ; Belov, Dmitri ; Rong, Ling Ling ; Sousa, Monica ; Andrassy, Martin ; Marso, Steven P. ; Duda, Stephan ; Arnold, Bernd ; Liliensiek, Birgit ; Nawroth, Peter P. ; Stern, David ; Schmidt, Ann Marie ; Naka, Yoshifumi. / Central role of RAGE-dependent neointimal expansion in arterial restenosis. In: Journal of Clinical Investigation. 2003 ; Vol. 111, No. 7. pp. 959-972.
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