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  • Low-molecular-weight fucoidan protects endothelial function and ameliorates basal hypertension in diabetic Goto-Kakizaki rats.

Low-molecular-weight fucoidan protects endothelial function and ameliorates basal hypertension in diabetic Goto-Kakizaki rats.

Laboratory investigation; a journal of technical methods and pathology (2014-03-13)
Wentong Cui, Yuanyuan Zheng, Quanbin Zhang, Jing Wang, Limin Wang, Wenzhe Yang, Chenyang Guo, Weidong Gao, Xiaomin Wang, Dali Luo
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Fucoidan from Macrocystis pyrifera, ≥85%
Sigma-Aldrich
Nitric Oxide Synthase, Inducible from mouse, recombinant, expressed in E. coli, buffered aqueous solution
Sigma-Aldrich
Fucoidan from Fucus vesiculosus, Crude
Sigma-Aldrich
Fucoidan from Undaria pinnatifida, ≥95%
Sigma-Aldrich
Fucoidan from Fucus vesiculosus, ≥95%