DNA aptamer raised against advanced glycation end products inhibits neointimal hyperplasia in balloon-injured rat carotid arteries.
BACKGROUND
Advanced glycation end products (AGE) and their receptor (RAGE) interaction elicit inflammatory and proliferative reactions in arteries, thus playing a role in cardiovascular disease. We have recently found that high-affinity DNA aptamer directed against AGE (AGE-aptamer) prevents the progression of experimental diabetic nephropathy by blocking the harmful actions of AGEs in the kidney. However, effects of AGE-aptamer on vascular injury remain unknown. In this study, we examined whether and how AGE-aptamer inhibits neointimal hyperplasia in balloon-injured rat carotid arteries.


METHODS
Male Wistar rats (weighting ca. 400 g at 11 weeks old) were anesthetized with sodium pentobarbital. The left common carotid artery was balloon-injured 3 times with 2F Fogaty catheter inserted through the femoral artery. Then the rats received continuous intraperitoneal infusion (3 μg/day) of either AGE-aptamer or control-aptamer by an osmotic mini pump for 2 weeks. 14 days after the procedure, the left common carotid arteries were excised for morphometric, immunohistochemical and western blot analyses.


RESULTS
Compared with control-aptamer, AGE-aptamer significantly suppressed neointima formation after balloon injury and reduced AGE accumulation, oxidative stress generation, proliferation cell nuclear antigen-positive area, macrophage infiltration, RAGE and platelet-derived growth factor-BB (PDGF-BB) expression levels in balloon-injured carotid arteries.


CONCLUSIONS
The present study suggests that AGE-aptamer could prevent balloon injury-induced neointimal hyperplasia by reducing PDGF-BB and macrophage infiltration via suppression of the AGE-RAGE-mediated oxidative stress generation. AGE-aptamer might be a novel therapeutic strategy for suppressing neointima formation after balloon angioplasty.
Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan.
Ayako
A
Ojima
Department of Chemistry, Kurume University School of Medicine, Kurume, Japan.
Eriko
E
Oda
Department of Chemistry, Kurume University School of Medicine, Kurume, Japan.
Yuichiro
Y
Higashimoto
Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan.
Takanori
T
Matsui
Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan. Electronic address: shoichi@med.kurume-u.ac.jp.
Sho-ichi
S
Yamagishi
D000818:Animals; D052157:Aptamers, Nucleotide / Q000008:administration & dosage*; D020212:Carotid Artery Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017127:Glycation End Products, Advanced / Q000008:administration & dosage* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006965:Hyperplasia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D058426:Neointima / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D052157:Aptamers, Nucleotide; D017127:Glycation End Products, Advanced
AGE-aptamer; Balloon injury; Neointimal hyperplasia; RAGE