Inhibition of the Association of Proteoglycans with Cultured Vascular Endothelial Cell Layers by Calcium and Sodium Spirulan.

Kaji, Tatsuru; Shimada, Satomi; Yamamoto, Chika; Fujiwara, Yasuyuki; Lee, Jung‐Bum; Hayashi, Toshimitsu

doi:10.1248/jhs.48.250

Cited by 12 publications

(8 citation statements)

References 24 publications

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“…6) In addition, Na-SP can stimulate the release of anticoagulant heparan 7) and dermatan 8) sulfate proteoglycans from vascular endothelial cell layers. 9) These results indicate that Na-SP may have beneficial effects as an anticoagulant agent on the blood coagulation-fibrinolytic system through not only activation of heparin cofactor II but also influence upon vascular endothelial cell functions.…”

Section: Introductionmentioning

confidence: 71%

Differential Effects of Sodium Spirulan on the Secretion of Fibrinolytic Proteins from Vascular Endothelial Cells: Enhancement of Plasminogen Activator Activity

Yamamoto

Nakamura

Shimada

et al. 2003

JOURNAL OF HEALTH SCIENCE

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Sodium spirulan (Na-SP) is a sulfated polysaccharide with M r ~220000 isolated from the blue-green alga Spirulina platensis. Na-SP influences the blood coagulation-fibrinolytic system by activation of heparin cofactor II in vitro, although it has been incompletely understood whether the polysaccharide can act on vascular endothelial cell functions. In the present study, we investigated the effects of Na-SP on the fibrinolytic activity of human coronary endothelial cells in a culture system. It was found that Na-SP enhances the activity of tissue-type and urokinase-type plasminogen activators in the conditioned medium of the cells through induction of urokinase-type plasminogen activator secretion and inhibition of plasminogen activator inhibitor type 1 (PAI-1) secretion. The inhibitory effect of Na-SP on PAI-1 secretion was maintained even when sodium ion was removed or replaced by calcium ion, while it disappeared with desulfation, indicating that metal ion is not required but the sulfate group is essential for the inhibition of endothelial PAI-1 secretion by Na-SP. The present study revealed that Na-SP not only shows a strong antithrombin effect through activation of heparin cofactor II but also exhibits a fibrinolytic property through differential effects on endothelial fibrinolytic protein secretion.

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Section: Introductionmentioning

confidence: 71%

Differential Effects of Sodium Spirulan on the Secretion of Fibrinolytic Proteins from Vascular Endothelial Cells: Enhancement of Plasminogen Activator Activity

Yamamoto

Nakamura

Shimada

et al. 2003

JOURNAL OF HEALTH SCIENCE

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“…18) Although not only Na-SP but also other particular polysaccharides such as heparin, dextran sulfate and hyaluronan can stimulate endothelial PG release, 19) it has been unclear whether these polysaccharides act on the release of both HSPGs and CS/DS PGs, as does Na-SP. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…These results support the hypothesis that Na-SP exhibits an anticoagulant activity through modulation of vascular endothelial cell functions such as PG metabolism. 18) Not only Na-SP, but also heparin, dextran sulfate and hyaluronan, stimulates the release of PGs from vascular endothelial cell layers. 19) However, it was shown that the stimulation by heparin, dextran sulfate and hyaluronan occurred mainly in the HSPG release, whereas that by Na-SP did in both HSPGs and CS/DS PGs.…”

Section: Discussionmentioning

confidence: 99%

“…17) It was shown that Na-SP stimulates the endothelial PG release as does heparin 18) ; the stimulatory effect requires both the sulfate group and a sodium ion. 19) However, the type(s) of endothelial PGs whose release is stimulated by Na-SP has not been identified yet.…”

Section: )mentioning

confidence: 99%

“…We hypothesized that Na-SP may influence the metabolism of endothelial PGs, since heparin has a stimulatory effect on the release of PGs from vascular endothelial cells. 17) It was shown that Na-SP stimulates the endothelial PG release as does heparin 18) ; the stimulatory effect requires both the sulfate group and a sodium ion. 19) However, the type(s) of endothelial PGs whose release is stimulated by Na-SP has not been identified yet.…”

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Proteoglycans Released from Cultured Bovine Aortic Endothelial Cell Layers by Sodium Spirulan Are Both Perlecan and Biglycan

Yamamoto

Shimada

Fujiwara

et al. 2005

Biological & Pharmaceutical Bulletin

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Proteoglycans (PGs) are macromolecules that are composed of a core protein and one or more glycosaminoglycan (GAGs) side chains in a common feature. 1) In the vascular tissue, PGs are involved in the regulation of vascular properties such as permeability, lipid metabolism, hemostasis, thrombosis, and extracellular matrix assembly. [2][3][4][5] In addition, PGs influence the regulation of vascular endothelial and smooth muscle cell function mediated by growth factors 6) and cytokines. 7) There are two types of PGs classified by the structure of GAG chains: one is heparan sulfate PGs (HSPGs) and the other is chondroitin/dermatan sulfate PGs (CS/DS PGs). Vascular endothelial cells predominantly synthesize and secrete a large HSPG, perlecan,8) and a small CS/DS PG, biglycan. 9)Perlecan exhibits antithrombin activity through the activation of antithrombin III 10) by heparin-like sequences in the heparan sulfate chains.11) On the other hand, the antithrombin activity of biglycan is achieved by the activation of heparin cofactor II by the dermatan sulfate chains.12) It is therefore suggested that PGs synthesized and secreted by vascular endothelial cells contribute to local anticoagulant activity on the endothelium.Sodium spirulan (Na-SP) is a sulfated polysaccharide isolated as an antiviral agent from a hot water extract of the blue-green alga Spirulina platensis. 13,14) On the other hand, Na-SP exhibits antithrombin activity in vitro in a fashion different from heparin, 15) suggesting that Na-SP may be an agent that can control anticoagulant activity in the blood. In addition, we found that Na-SP enhances the fibrinolytic activity of the cells through inhibition of plasminogen activator inhibitor-1 secretion.16) This indicates that Na-SP can modulate the anticoagulant and fibrinolytic properties of vascular endothelial cells. We hypothesized that Na-SP may influence the metabolism of endothelial PGs, since heparin has a stimulatory effect on the release of PGs from vascular endothelial cells.17) It was shown that Na-SP stimulates the endothelial PG release as does heparin 18) ; the stimulatory effect requires both the sulfate group and a sodium ion. 19) However, the type(s) of endothelial PGs whose release is stimulated by Na-SP has not been identified yet. In the present study, we suggest that Na-SP-releasable PGs in vascular endothelial cells are both perlecan and biglycan with the intact structure, although the core proteins may be partially degraded. MATERIALS AND METHODSMaterials Vascular endothelial cells derived from bovine aorta were purchased from Dainippon Pharmaceutical (Osaka, Japan). Na-SP was purified as described previously.1,2) Dulbecco's modified Eagle's medium and fetal bovine serum were from Nissui Pharmaceutical (Tokyo, Japan) and Equitech-Bio (Kerrville, TX, U.S.A.), respectively. ASF 301 medium was from Ajinomoto (Tokyo, Japan); tissue culture dishes and plates were from Asahi Technoglass (Chiba, Japan Sodium spirulan (Na-SP) is a sulfated polysaccharide isolated from the blue-green alga Spiruli...

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Cyanobacterial Extracellular Polymeric Substances (EPS)

Mota¹,

Flores²,

Tamagnini³

2021

Polysaccharides of Microbial Origin

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Inhibition of the Association of Proteoglycans with Cultured Vascular Endothelial Cell Layers by Calcium and Sodium Spirulan.

Cited by 12 publications

References 24 publications

Differential Effects of Sodium Spirulan on the Secretion of Fibrinolytic Proteins from Vascular Endothelial Cells: Enhancement of Plasminogen Activator Activity

Differential Effects of Sodium Spirulan on the Secretion of Fibrinolytic Proteins from Vascular Endothelial Cells: Enhancement of Plasminogen Activator Activity

Proteoglycans Released from Cultured Bovine Aortic Endothelial Cell Layers by Sodium Spirulan Are Both Perlecan and Biglycan

Cyanobacterial Extracellular Polymeric Substances (EPS)

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