Effect of chronic subcutaneous or intramural administration of heparin on femoral artery restenosis after balloon angioplasty in hypercholesterolemic rabbits. A quantitative angiographic and histopathological study.

Gimple, Lawrence W.; Gertz, S. David; Haber, Howard L.; Ragosta, Michael; Powers, Eric R.; Roberts, William C.; Sarembock, Ian J.

doi:10.1161/01.cir.86.5.1536

Cited by 50 publications

(23 citation statements)

References 31 publications

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“…The data presented indicated that LMW fucoidan reduced neointimal hyperplasia by Ϸ60% and increased the luminal area by Ϸ25%, making this compound one of the most efficient ever tested in experimental restenosis by using a noncontinuous administration regimen. 16 In contrast to heparin tested in animal models of balloon angioplasty 17,18 and clinical trials, 19 HMW fucoidan was already used at high dose (25 mg/kg in mice, 20 100 mg/kg in rats, 21 and 10 mg/kg per hour in rabbits 22 ) without bleeding. In the present study, the fraction of LMW fucoidan (8 kDa), used in rabbits at low dose (5 mg/kg), exhibited no anticoagulant activity in vivo.…”

Section: Discussionmentioning

confidence: 99%

Low Molecular Weight Fucoidan Prevents Neointimal Hyperplasia in Rabbit Iliac Artery In-Stent Restenosis Model

Deux

Meddahi‐Pellé

Blanche

et al. 2002

ATVB

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Objective-Smooth muscle cell (SMC) proliferation within the intima is regulated by heparan sulfates. We studied a low molecular weight (LMW) fucoidan (sulfated polysaccharide from brown seaweed) on SMC proliferation in vitro and intimal hyperplasia in vivo. Methods and Results-In vitro study revealed that LMW fucoidan reduces rabbit SMC proliferation and is internalized in SMC perinuclear vesicles. On rabbit iliac arteries perfused in vivo with fluorolabeled LMW fucoidan after angioplasty, the labeling was mainly located on sites of injury. Pharmacokinetic studies showed that LMW fucoidan exhibited in rats an elimination half-life of 56Ϯ25 minutes (nϭ8) after intravenous administration and a constant plasma rate for Ն6 hours after intramuscular administration. After stent implantation in their iliac arteries, rabbits were also treated with LMW fucoidan (5 mg/kg IM twice a day Key Words: fucoidan Ⅲ hyperplasia Ⅲ restenosis Ⅲ stent Ⅲ vascular smooth muscle cell proliferation I ntimal hyperplasia due to migration and proliferation of smooth muscle cells (SMCs) from the media to the intima is a major component of restenosis after stent implantation. 1,2 Polysaccharides constitute a large family of molecules capable of developing molecular interactions with cellular targets within the arterial wall. 3 For instance, heparin, a natural sulfated polysaccharide, displays pleiotropic effects independent of the anticoagulant activity, including SMC growth inhibition, 4 anti-inflammatory activity, 5 and growth factor protection. 6 Fucoidan is a sulfated polysaccharide extracted from brown seaweed that reduces rat SMC proliferation in vitro in a more intensive manner than heparin. 7 We recently succeeded in producing and characterizing new homogeneous fractions of low molecular weight (LMW) fucoidan with low anticoagulant activity.The aims of the present study were to investigate the ability of LMW fucoidan to regulate vascular SMCs. For this purpose, we first tested the ability of LMW fucoidan to inhibit rabbit SMC proliferation in vitro. We explored the pharmacokinetics of LMW fucoidan injected in rats and the effect of LMW fucoidan on intimal hyperplasia. The results described below indicate that LMW fucoidan is a strong inhibitor of intimal hyperplasia and may be potentially relevant for the treatment of in-stent restenosis. Methods PolysaccharidesLMW fucoidan was isolated and hydrolyzed by a radical depolymerization process 8 from high molecular weight (HMW) extracts of brown marine algae. The characteristics of LMW fucoidan according to previously reported analytical methods 9 are as follows: weightaverage molecular mass 8Ϯ1 kDa; fucose content 35% (wt/wt); uronic acid content 3% (wt/wt); and sulfate content 34% (wt/wt). The anticoagulant activity in vitro of the LMW fucoidan was measured by an activated partial thromboplastin time (APTT), and the amount of LMW fucoidan required to obtain an APTT of 80 seconds (control 40 seconds) was 25 g/mL. 10 The anticoagulant activity in vivo of LMW fucoidan was measured in rabbit...

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Section: Discussionmentioning

confidence: 99%

Low Molecular Weight Fucoidan Prevents Neointimal Hyperplasia in Rabbit Iliac Artery In-Stent Restenosis Model

Deux

Meddahi‐Pellé

Blanche

et al. 2002

ATVB

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“…However, the rabbit model we used has been demonstrated to have several features in common with human atherosclerosis and to be reproducible. 28,29 The combination of initial balloon injury with high-cholesterol diet results in severe atherosclerotic lesions and very high cholesterol levels and is associated with a significant morbidity rate in the animals. This model produces lesions that resemble those in humans more closely than lesions produced by hypercholesterolemia alone.…”

Section: Discussionmentioning

confidence: 99%

Dietary Lipid Lowering Modifies Plaque Phenotype in Rabbit Atheroma After Angioplasty

et al. 2003

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Background-Tissue factor (TF), the main initiator of blood coagulation, is involved in cellular migration and angiogenesis processes. TF is expressed strongly in lipid-rich plaques and probably plays an important role in the thrombotic complications of plaque rupture. This study analyzes the effect of dietary lipid lowering on TF expression and cellular modifications in angioplasty-induced rabbit plaque rupture. Methods and Results-After experimental plaque rupture by balloon angioplasty in atheromatous rabbits, animals were assigned a 0.2% or a 2% cholesterol diet, and the TF content of arterial wall and the associated histological modifications were analyzed after 4 weeks. Early effects of lipid lowering were observed: The increase of TF expression in the vascular wall was stronger in the 2% than in the 0.2% cholesterol diet group (iliac arteries: 1226Ϯ308 versus 72Ϯ29 mU TF/g artery, PϽ0.005). Immunohistochemistry indicated that TF expression was associated with sprout of neovessels, which was more pronounced in the 2% than in the 0.2% cholesterol group. Conclusions-This study shows that dietary lipid lowering decreases the thrombotic potential of ruptured atherosclerotic plaques through TF decrease. Moreover, high TF expression is associated with marked angiogenesis in the vascular wall, which is reduced by lipid lowering. These results provide further arguments for strong dietary lipid lowering to reduce plaque instability and thrombogenicity.

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“…26 %CSAN-P was calculated as the area bound by the internal elastic lamina minus luminal area times 100 divided by the area bound by the internal elastic lamina.…”

Section: Histomorphometrymentioning

confidence: 99%

Induction of IG9 Monocyte Adhesion Molecule Expression in Smooth Muscle and Endothelial Cells After Balloon Arterial Injury in Cholesterol-Fed Rabbits

Calderon

Gertz

Sarembock

et al. 2000

ATVB

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Abstract-The expression of monocyte-specific adhesion molecules and chemokines by cell types within the vessel wall plays an important role in foam cell accumulation during atherosclerotic plaque development. We previously identified IG9, a novel monocyte adhesion protein that is expressed on endothelial cells (ECs) overlying human and rabbit advanced atherosclerotic plaques. The present study was designed to determine the temporal and spatial expression of IG9 and the chemokine, monocyte chemoattractant protein-1 (MCP-1), after balloon injury with (double injury) or without (single injury) prior air desiccation EC injury in the femoral arteries of rabbits fed a high-cholesterol diet. By immunohistochemical analyses, intense reactivity with monoclonal antibodies to IG9 and MCP-1 was detected 24 hours after single injury in medial smooth muscle cells (SMCs) and in SMCs of adventitial microvessels. However, monocyte infiltration of the tunica media was minimal or not detected in these sections. IG9 and MCP-1 antibody reactivity in vessel sections 28 days after single injury and 24 hours, 7 days, and 28 days after double injury was localized to medial and neointimal SMCs, foam cells, and luminal ECs overlying the plaques. Uninjured rabbit (cholesterol or normal diet) vessel sections exhibited minimal IG9 and MCP-1 immunostaining. In vitro studies using human aortic SMCs demonstrated IG9 protein induction after 24 hours of treatment with platelet-derived growth factor-BB and interferon-␥ or epidermal growth factor. IG9 expression was further increased by pretreatment of SMCs with the proatherogenic lipid, minimally oxidized low density lipoprotein. After balloon injury (24 hours Key Words: arterial injury Ⅲ atherosclerosis Ⅲ smooth muscle Ⅲ adhesion molecules Ⅲ LDL, minimally oxidized or modified T he adherence of circulating monocytes to endothelial cells (ECs) is one of the earliest events in the development of atherosclerotic plaques. [1][2][3] Injury to the vascular endothelium induces EC dysfunction and promotes an inflammatory response characterized by the adherence of monocytes and T lymphocytes to the vessel wall. [1][2][3][4] On entering the subendothelial space, monocytes take up lipids, become activated, and release inflammatory and chemotactic molecules, including the cytokine, tumor necrosis factor-␣ (TNF-␣), 5,6 and the chemokine, monocyte chemoattractant protein-1 (MCP-1). 7,8 Chemokine expression contributes to the recruitment of additional monocytes (and T lymphocytes) into the developing lesion, and inflammatory mediators produced by the infiltrating leukocytes stimulate resident cells within the vessel wall to secrete additional proatherogenic molecules, including growth-regulatory factors, cytokines, and other chemokines. These molecules promote medial smooth muscle cell (SMC) migration and proliferation and the continued influx of monocytes and T lymphocytes, thereby amplifying this inflammatory process and promoting neointimal hyperplasia. 3,9 An understanding of the mechanisms involved in the ...

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Effect of chronic subcutaneous or intramural administration of heparin on femoral artery restenosis after balloon angioplasty in hypercholesterolemic rabbits. A quantitative angiographic and histopathological study.

Cited by 50 publications

References 31 publications

Low Molecular Weight Fucoidan Prevents Neointimal Hyperplasia in Rabbit Iliac Artery In-Stent Restenosis Model

Low Molecular Weight Fucoidan Prevents Neointimal Hyperplasia in Rabbit Iliac Artery In-Stent Restenosis Model

Dietary Lipid Lowering Modifies Plaque Phenotype in Rabbit Atheroma After Angioplasty

Induction of IG9 Monocyte Adhesion Molecule Expression in Smooth Muscle and Endothelial Cells After Balloon Arterial Injury in Cholesterol-Fed Rabbits

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