| Low-molecular-weight fucoidan protects endothelial function and ameliorates basal hypertension in diabetic Goto-Kakizaki rats | |
Cui, Wentong1; Zheng, Yuanyuan1; Zhang, Quanbin2; Wang, Jing2 ; Wang, Limin1; Yang, Wenzhe1; Guo, Chenyang1; Gao, Weidong3; Wang, Xiaomin4; Luo, Dali1; Luo, DL (reprint author), Capital Med Univ, Dept Pharmacol, St Youanmenwai,10 Xitoutiao, Beijing 100069, Peoples R China.
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| 2014-04-01 | |
| 发表期刊 | LABORATORY INVESTIGATION
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| 卷号 | 94期号:4页码:382-393 |
| 文章类型 | Article |
| 摘要 | Endothelial dysfunction, characterized by impairment of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) bioavailability, has been implicated in diabetic cardiovascular pathogenesis. In this study, low-molecular-weight fucoidan (LMWF), which has multiple biological activities including anti-inflammatory and anti-oxidative properties, was investigated for its protective effect against endothelial dysfunction in Goto-Kakizaki type 2 diabetic rats. LMWF (50, 100, or 200 mg/kg/day) or probucol (100 mg/kg/day) were given to diabetic rats for 12 weeks. Basal blood pressure, acetylcholine- or flow-mediated relaxation of mesenteric and paw arteries, endothelium-dependent dilation of aorta, eNOS phosphorylation, and NO production were measured using laser Doppler flowmetry, force myograph, hematoxylin and eosin staining, western blot analysis, and an NO assay. We found that LMWF robustly ameliorated the basal hypertension and impairment of endothelium-dependent relaxation in the aorta, as well as mesenteric and paw arteries in diabetic rats. In addition, the reduction in eNOS phosphorylation at Ser1177, eNOS expression, and NO production because of diabetes were partially reversed by LMWF treatment. However, probucol, a lipid-modifying drug with antioxidant properties, displayed only mild effects. Moreover, LMWF induced, in a dose-dependent manner, endothelium-dependent vasodilation and eNOS phosphorylation at Ser1177 in normal aorta, and also promoted Ser1177 phosphorylation and NO synthesis in primary cultured vasoendothelial cells. Thus, these data demonstrate for the first time that fucoidan protects vasoendothelial function and reduces basal blood pressure in type 2 diabetes rats via, at least in part, preservation of eNOS function. Fucoidan is therefore a potential candidate drug for protection of endothelium in diabetic cardiovascular complications. |
| 关键词 | Diabetes Endothelium-dependent Vasodilation Endothelial Nitric Oxide Synthase Low-molecular-weight Fucoidan Nitric Oxide |
| 学科领域 | Research & Experimental Medicine ; Pathology |
| DOI | 10.1038/labinvest.2014.12 |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000333574900003 |
| 引用统计 | |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://ir.qdio.ac.cn/handle/337002/24232 |
| 专题 | 海洋生物技术研发中心 |
| 通讯作者 | Luo, DL (reprint author), Capital Med Univ, Dept Pharmacol, St Youanmenwai,10 Xitoutiao, Beijing 100069, Peoples R China. |
| 作者单位 | 1.Capital Med Univ, Dept Pharmacol, Beijing 100069, Peoples R China 2.Chinese Acad Sci, Inst Oceanol, Qingdao, Peoples R China 3.Johns Hopkins Univ, Sch Med, Baltimore, MD USA 4.Capital Med Univ, Dept Physiol, Beijing 100069, Peoples R China |
| 推荐引用方式 GB/T 7714 | Cui, Wentong,Zheng, Yuanyuan,Zhang, Quanbin,et al. Low-molecular-weight fucoidan protects endothelial function and ameliorates basal hypertension in diabetic Goto-Kakizaki rats[J]. LABORATORY INVESTIGATION,2014,94(4):382-393. |
| APA | Cui, Wentong.,Zheng, Yuanyuan.,Zhang, Quanbin.,Wang, Jing.,Wang, Limin.,...&Luo, DL .(2014).Low-molecular-weight fucoidan protects endothelial function and ameliorates basal hypertension in diabetic Goto-Kakizaki rats.LABORATORY INVESTIGATION,94(4),382-393. |
| MLA | Cui, Wentong,et al."Low-molecular-weight fucoidan protects endothelial function and ameliorates basal hypertension in diabetic Goto-Kakizaki rats".LABORATORY INVESTIGATION 94.4(2014):382-393. |
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