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Alagebrium chloride, a novel advanced glycation end-product cross linkage breaker, inhibits neointimal proliferation in a diabetic rat carotid balloon injury model.

 Jin-Bae Kim  ;  Byeong-Wook Song  ;  Sungha Park  ;  Ki-Chul Hwang  ;  Bong-Soo Cha  ;  Yangsoo Jang  ;  Hyun-Chul Lee  ;  Moon-Hyoung Lee 
 KOREAN CIRCULATION JOURNAL, Vol.40(10) : 520-526, 2010 
Journal Title
Issue Date
Advanced glycation end-products ; Alagebrium ; Neointimal hyperplasia
BACKGROUND AND OBJECTIVES: Vascular perturbation induced by advanced glycation end-products (AGEs) leads to progression of atherosclerosis, plaque instability, and vascular inflammation, which results in a higher risk of neointimal proliferation. Here we investigated the inhibitory effect of alagebrium chloride (ALT-711), a breaker of AGE-based cross links, on neointimal proliferation in a carotid artery balloon injury model in diabetic rats induced by streptozotocin (STZ).

MATERIALS AND METHODS: Rat aortic vascular smooth muscle cells (RASMCs) were treated with 1-100 µM of alagebrium added 24 hours before the addition of AGEs. This in vivo study was done using 8-week-old male rats that were injected intraperitoneally with 80 mg/kg STZ. Sixteen weeks later, the diabetic rats were treated with 10 mg/kg alagebrium for 4 weeks, after which carotid artery balloon injury was induced. After 4 weeks, the animals were sacrificed for histological analysis.

RESULTS: Proliferation of RASMCs was significantly inhibited in alagebrium-treated cells. Alagebrium dose-dependently inhibited AGE-mediated formation of reactive oxygen species (ROS), extracellular signal-regulated kinase phosphorylation, and cyclooxygenase-2 expression. The cellular mechanisms of AGE-induced connective tissue and extracellular matrix expression were decreased in the alagebrium-treated group. This in vivo study shows that expression of AGE receptors and neointima hyperplasia are significantly suppressed in balloon-injured rats treated with alagebrium.

CONCLUSION: Alagebrium treatment in diabetic rats significantly inhibits neointimal hyperplasia after carotid balloon injury due to its inhibition of intracellular ROS synthesis, which results in inhibition of RASMCs proliferation
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10.4070 / kcj.2010.40.10.520
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Jin Bae(김진배)
Park, Sung Ha(박성하) ORCID logo https://orcid.org/0000-0001-5362-478X
Song, Byeong Wook(송병욱)
Lee, Moon-Hyoung(이문형) ORCID logo https://orcid.org/0000-0002-7268-0741
Lee, Hyun Chul(이현철)
Jang, Yang Soo(장양수) ORCID logo https://orcid.org/0000-0002-2169-3112
Cha, Bong Soo(차봉수) ORCID logo https://orcid.org/0000-0003-0542-2854
Hwang, Ki Chul(황기철)
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