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Updated: May 5, 2026

A Rat Carotid Balloon Injury Model to Test Anti-vascular Remodeling Therapeutics
Published on: September 19, 2016
Receptor for AGE (RAGE) mediates neointimal formation in response to arterial injury
Zhongmin Zhou1, Kai Wang, Marc S Penn
1Experimental Interventional Laboratory, Department of Cardiovascular Medicine, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
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.
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