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CardioVascular and Interventional Radiology

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01-12-2012 | Laboratory Investigation

Decreased Neointimal Extracellular Matrix Formation in RAGE-Knockout Mice After Microvascular Denudation

Authors: Gerd Grözinger, Jörg Schmehl, Rüdiger Bantleon, Rainer Kehlbach, Tarun Mehra, Claus Claussen, Benjamin Wiesinger

Published in: CardioVascular and Interventional Radiology | Issue 6/2012

Abstract

Purpose

To evaluate in vivo the role of RAGE (receptor for advanced glycated end products) in the development of restenosis and neointimal proliferation in RAGE-deficient knockout (KO) mice compared with wild-type (WT) mice in an animal model.

Materials and Methods

Sixteen WT and 15 RAGE-deficient mice underwent microvascular denudation of the common femoral artery under general anaesthesia. Contralateral arteries underwent a sham operation and served as controls. Four weeks after the intervention, all animals were killed, and paraformaldehyde-fixed specimens of the femoral artery were analysed with different stains (hematoxylin and eosin and Elastica van Gieson) and several different types of immunostaining (proliferating cell nuclear antigen, α-actin, collagen, von Willebrand factor, RAGE). Luminal area, area of the neointima, and area of the media were measured in all specimens. In addition, colony-formation assays were performed, and collagen production by WT smooth muscle cells (SMCs) and RAGE-KO SMCs was determined. For statistical analysis, P < 0.05 was considered statistically significant.

Results

Four weeks after denudation, WT mice showed a 49.6% loss of luminal area compared with 14.9% loss of luminal area in RAGE-deficient mice (sham = 0% loss) (P < 0.001). The neointima was 18.2 (*1000 μm² [n = 15) in the WT group compared with only 8.4 (*1000 μm² [n = 16]) in the RAGE-KO group. RAGE-KO SMCs showed significantly decreased proliferation activity and production of extracellular matrix protein.

Conclusion

RAGE may be shown to play a considerable role in the formation of neointima leading to restenosis after vascular injury.

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Title: Decreased Neointimal Extracellular Matrix Formation in RAGE-Knockout Mice After Microvascular Denudation
Authors: Gerd Grözinger
Jörg Schmehl
Rüdiger Bantleon
Rainer Kehlbach
Tarun Mehra
Claus Claussen
Benjamin Wiesinger
Publication date: 01-12-2012
Publisher: Springer-Verlag
Published in: CardioVascular and Interventional Radiology / Issue 6/2012
Print ISSN: 0174-1551
Electronic ISSN: 1432-086X
DOI: https://doi.org/10.1007/s00270-011-0319-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Decreased Neointimal Extracellular Matrix Formation in RAGE-Knockout Mice After Microvascular Denudation

Abstract

Purpose

Materials and Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Materials and Methods

Results

Conclusion

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