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The role of RAGE in aminoguanidine-induced suppression of venous intimal hyperplasia in diabetic rats.

Abstract：

:Intimal hyperplasia is one of the major pathological processes in vein graft failure with diabetes mellitus. In this study, we tested the hypothesis that the suppressive effect of aminoguanidine on intimal hyperplasia is mediated by downregulated expression of advanced glycation end products (AGE) and its receptor (RAGE) in streptozotocin-induced diabetes. To induce intimal hyperplasia, autologous external jugular vein was grafted into the infrarenal abdominal aorta in 52 male Sprague-Dawley rats. In diabetic rats, distilled water with or without aminoguanidine was administrated, whereas nondiabetic rats were given distilled water alone. Vein grafts were harvested at 1 and 4 weeks after surgery for morphological analysis and semiquantitative reverse transcriptase polymerase chain reaction analysis for RAGE and nuclear factor kappaB (NF-kappaB) p65. Serum AGE level was determined by fluorospectrophotometry. Compared to nondiabetic rats, serum levels of AGE in diabetic rats administrated distilled water were significantly increased. The expression of RAGE and NF-kappaB p65, the ratio of intima to media area, and the percentage of proliferating cell nuclear antigen (PCNA)-positive cells were significantly increased in the vein graft. In diabetic rats treated with aminoguanidine, serum AGE level NF-kappaB p65 expression, the ratio of intima to media area, and the percentage of PCNA-positive cells in the vein graft were all significantly decreased. However, no difference in the expression of RAGE was found compared to the diabetic group given distilled water. Our data suggest that AGE-RAGE may play a key role in venous intimal hyperplasia in diabetes mellitus and aminoguanidine suppressed intimal hyperplasia by inhibiting this pathway.

journal_name

Ann Vasc Surg

journal_title

Annals of vascular surgery

authors

Wang X,Diao Y,Zhang H,Huo X,Zhang Q

doi

10.1016/j.avsg.2008.09.004

subject

Has Abstract

pub_date

2009-03-01 00:00:00

pages

246-54

issue

2

eissn

0890-5096

issn

1615-5947

pii

S0890-5096(08)00341-5

journal_volume

23

pub_type

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