Differential Inhibition of Neointimal Thickening After Balloon Injury in the Rabbit Aorta by Glycosaminoglycans

SummaryThe behavior of 125I-labeled recombinant hirudin towards the uninjured and de-endothelialized rabbit aorta wall has been studied in vitro and in vivo to determine its usefulness as an indicator of thrombin activity associated with the aorta wall. Thrombin adsorbed to either sulfopropyl-Sephadex or heparin-Sepharose bound >95% of 125I-r-hirudin and the complex remained bound to the matrix. Binding of 125I-r-hirudin to the exposed aorta subendothelium (intima-media) in vitro was increased substantially if the tissue was pre-treated with thrombin; the quantity of l25I-r-hirudin bound to the de-endothelialized intima-media (i.e. balloon-injured in vitro) correlated positively with the quantity of bound 131I-thrombin (p <0.01). Aortas balloon-injured in vivo were measured for thrombin release from, and binding of 125I-r-hirudin to, the de-endothelialized intimal surface in vitro; 125I-r-hirudin binding correlated with the amount of active thrombin released (p <0.001). Uptake of 125I-r-hirudin by the aorta wall in vivo was proportional to the uptake of 131I-fibrinogen (as an indicator of thrombin activity) before and after balloon injury. After 30 min in the circulation, specific 125I-r-hirudin binding to the uninjured and de-endo- thelialized (at 1.5 h after injury) aorta wall was equivalent to 3.4 (± 2.5) and 25.6 (±18.1) fmol of thrombin/cm2 of intima-media, respectively. Possibly, only hirudin-accessible, glycosaminoglycan-bound thrombin is measured in this way.

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Thrombogenicity of the Injured Vessel Wall – Role of Antithrombin and Heparin

Thrombosis and Haemostasis ◽

10.1055/s-0038-1642399 ◽

1994 ◽

Vol 71 (01) ◽

pp. 147-153 ◽

Cited By ~ 22

Author(s):

Siw Frebelius ◽

Ulf Hedin ◽

Jesper Swedenborg

Keyword(s):

Vessel Wall ◽

Antithrombin Iii ◽

Rabbit Aorta ◽

Continuous Treatment ◽

Balloon Injury ◽

Coagulant Activity ◽

Risk For Thrombosis ◽

Inhibition Of Thrombin

SummaryThe thrombogenicity of the vessel wall after endothelial denudation is partly explained by an impaired inhibition of thrombin on the subendothelium. We have previously reported that thrombin coagulant activity can be detected on the vessel wall after balloon injury in vivo. The glycosaminoglycans of the subendothelium differ from those of the endothelium and have a lower catalyzing effect on antithrombin III, but inhibition of thrombin can still be augmented by addition of antithrombin III to the injured vessel surface.In this study the effect of antithrombin III and heparin on thrombin coagulant activity on the vessel wall was studied after in vivo balloon injury of the rabbit aorta using biochemical and immunohistochemical methods and thrombin was analysed after excision of the vessel. Continuous treatment with heparin, lasting until sacrifice of the animal, or treatment with antithrombin III resulted in significant reduction of thrombin coagulant activity on the injured aorta. Heparin given only in conjunction with the injury did not prevent thrombin coagulant activity or deposition of fibrin on the surface.The capacity of the injured vessel wall to inhibit thrombin in vitro was improved on aortic segments obtained from animals receiving antithrombin III but not from those given heparin. It is concluded that treatment with antithrombin III interferes with thrombin appearance on the vessel wall after injury and thereby reduces the risk for thrombosis.

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17β-estradiol, gender independently, reduces atheroma development but not neointimal proliferation after balloon injury in the rabbit aorta

Atherosclerosis ◽

10.1016/s0021-9150(00)00446-9 ◽

2001 ◽

Vol 154 (1) ◽

pp. 39-49 ◽

Cited By ~ 10

Author(s):

G Finking

Keyword(s):

Rabbit Aorta ◽

Balloon Injury ◽

Neointimal Proliferation ◽

17Β Estradiol

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Probucol inhibits neointimal thickening and macrophage accumulation after balloon injury in the cholesterol-fed rabbit.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.89.23.11312 ◽

1992 ◽

Vol 89 (23) ◽

pp. 11312-11316 ◽

Cited By ~ 89

Author(s):

G. A. Ferns ◽

L. Forster ◽

A. Stewart-Lee ◽

M. Konneh ◽

J. Nourooz-Zadeh ◽

...

Keyword(s):

Balloon Injury ◽

Neointimal Thickening ◽

Macrophage Accumulation

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Effects of TH-142177 on angiotensin II-induced proliferation, migration and intracellular signaling in vascular smooth muscle cells and on neointimal thickening after balloon injury

Life Sciences ◽

10.1016/s0024-3205(99)00153-8 ◽

1999 ◽

Vol 64 (22) ◽

pp. 2061-2070 ◽

Cited By ~ 26

Author(s):

Yoshihisa Nozawa ◽

Naosuke Matsuura ◽

Hidekazu Miyake ◽

Shizuo Yamada ◽

Ryohei Kimura

Keyword(s):

Smooth Muscle ◽

Angiotensin Ii ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Vascular Smooth Muscle Cells ◽

Intracellular Signaling ◽

Muscle Cells ◽

Balloon Injury ◽

Neointimal Thickening

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The interaction of platelets with aortic subendothelium: inhibition of adhesion and secretion by prostaglandin I2

Blood ◽

10.1182/blood.v58.2.198.198 ◽

1981 ◽

Vol 58 (2) ◽

pp. 198-205 ◽

Cited By ~ 42

Author(s):

B Adelman ◽

MB Stemerman ◽

D Mennell ◽

RI Handin

Keyword(s):

Platelet Aggregation ◽

Aortic Wall ◽

Ex Vivo ◽

Rabbit Aorta ◽

Platelet Factor 4 ◽

Direct Immunofluorescence ◽

Balloon Injury ◽

Prostaglandin I2 ◽

Platelet Factor ◽

Reduced Surface

Abstract We have studied the effect of prostaglandin I2 on platelet turnover, attachment to the subendothelium, and secretion following balloon deendothelialization of the rabbit aorta. Survival of 51Cr-labeled platelets in the balloon-injured animals remained normal. Thirty minutes after injury, there were 4.52 X 10(6) platelets/sq cm attached to the aortic surface, which was 87% covered by platelets. Although plasma platelet factor 4, as measured by radioimmunoassay, did not rise above the normal level of 6.8 +/- 2.6 ng/ml (mean +/- SEM) during the first hour after balloon injury, platelet factor 4 antigen was detected within the vessel wall by direct immunofluorescence within 30 min of injury. An infusion of 650–850 ng/kg/min prostaglandin I2 completely inhibited platelet aggregation and reduced surface coverage by 84% and platelet attachment by 63%. Animals given 50–100 ng/kg/min prostaglandin I2, which only partially inhibited platelet aggregation, had 70% of the aortic surface covered by platelets. Platelet factor 4 antigen was also detected within the aortic wall. Platelet attachment was normal in animals that had been given 850 ng/kg/min prostaglandin I2 prior to balloon injury but sacrificed after the infusion was stopped and ex vivo platelet aggregation had returned to normal.

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