|
Accession number;01A0391386
|
| Title;Advanced Glycation End Products Inhibit Endothelial Glycosaminoglycan Production and DNA Synthesis. |
| Author;
KAWASUMI MASAHIKO
(Juntendodai Naikagaku)
MITSUMATA MASAKO
(Yamanashiidai Byorigakukozadaiichikyoshitsu)
SHIMADA SATOSHI
(Juntendodai Naikagaku)
ARISAKA TOMOYUKI
(Juntendodai Naikagaku)
YOSHIDA YOJI
(Yamanashiidai Byorigakukozadaiichikyoshitsu)
KAWAMORI RYUZO
(Juntendodai Naikagaku)
|
Journal Title;Journal of the Japan Diabetic Society
|
Journal Code:Z0279B
|
ISSN:0021-437X
|
|
VOL.44;NO.2;PAGE.115-120(2001)
|
| Figure&Table&Reference;FIG.4, REF.27 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;Vascular endothelial dysfunction in diabetic patients is suspected of being induced by advanced glycation end products (AGES). Recent studies have indicated that heparan sulfate proteoglycan, which is a major component of the glycosaminoglycans (GAGs) synthesized by endothelial cells (ECs), regulates anticoagulant activity by binding with antithrombin III. We therefore examined the effects of AGES on GAG synthesis and DNA synthesis by ECs. After incubating porcine aortic ECs in serum-free medium containing AGE-modified bovine serum albumin (AGE-BSA), synthesis of GAGs and DNA was assayed on the basis of [35S]-sulfate and [3H]-thymidine incorporation, respectively. Both the synthesis and secretion of GAGs by ECs were significantly reduced after AGE-BSA treatment. After ECs were exposed to 1mg/ml AGE-BSA for 55h, GAG synthesis was 86% of that in cells incubated with unmodified BSA (p<0.05), and it declined to 75% at 73h (p<0.01). After exposure to 0.5mg/ml AGE-BSA for 78h, GAG synthesis was 87% of the control level (p<0.05), and it fell to 84% in the presence of 1mg/ml AGE-BSA (p<0.05). Treatment with AGE-BSA for 48-60h also reduced [3H]-thymidine incorporation by ECs to 68-44% of the control level (p<0.01). The changes induced by AGE-BSA treatment were inhibited by an antioxidant (probucol). These results suggest that AGEs suppress GAG and DNA synthesis by ECs through oxidative stress and induce endothelial dysfunction by inhibiting endothelial anticoagulant activity. (author abst.) |
|
|
|
Related Articles;
|
