α8β1 Integrin is up-regulated in the neointima concomitant with late luminal loss after balloon injury

SummaryThis study aimed to investigate the effect of percutaneous endoluminal arterial cryoenergy immediately after balloon angioplasty on vascular remodeling. Restenosis, the main complication after coronary artery angioplasty, is a complex phenomenon in which vascular remodeling plays a prominent role. Observations of reduced scarring in freeze-induced wounds suggest potential value for cryoenergy in the prevention of restenosis. Juvenile swine underwent a first oversized balloon injury in both carotid arteries (CA) (3 injury sites/artery) and a second injury at day 14. At that time, one CA was randomly assigned to endoluminal cryoenergy of the sequential segments (proximal, medial, distal) at −15ºC, −30ºC, and −50ºC for 120 sec, and the other CA was used as control. Animals were sacrificed 28 days after the second procedure. Compared with intact reference segments, angioplasty reduced both the luminal (LA) and the external elastic lamina (EEL) areas from 6.66±0.59 to 3.13±0.54 mm2 (p<0.05) and from 8.81±0.81 to 6.48±0.52 mm2 (p<0.05), respectively. Cryoenergy, at the temperature with maximal benefits (-50°C), caused a temperature-related protection, as the LA was maintained (6.79±0.89 versus 7.18± 0.78 mm2 for reference) and the EEL area increased from 9.12±0.78 to 12.98±1.07 mm2, p<0.05. Moreover, cryoenergy increased the density of collagen III (p<0.05) which correlated with the maintenance of the LA (r=0.8045, p<0.009). Cryoenergy prevents late luminal loss after double-injury angioplasty by improving vascular remodeling, and is an interesting new therapeutic approach for the prevention of restenosis after angioplasty. The increased synthesis of collagen III appears to be involved in this phenomenon and could be a potential method of stabilizing the vulnerable plaque.

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Cyclic Thermal Treatment of Coronary Arteries Limits Smooth Muscle Cell Proliferation Following Balloon Injury: Results in a Porcine Coronary Organ Culture System

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(97)84149-6 ◽

1998 ◽

Vol 31 (2) ◽

pp. 102A

Author(s):

K Miyauchi

Keyword(s):

Cell Proliferation ◽

Smooth Muscle ◽

Thermal Treatment ◽

Organ Culture ◽

Smooth Muscle Cell ◽

Muscle Cell ◽

Coronary Arteries ◽

Culture System ◽

Balloon Injury ◽

Organ Culture System

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

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(97)83803-x ◽

1998 ◽

Vol 31 (2) ◽

pp. 21A ◽

Cited By ~ 1

Author(s):

D Schwartz

Keyword(s):

Rabbit Aorta ◽

Differential Inhibition ◽

Balloon Injury ◽

Neointimal Thickening

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Radiolabeled r-Hirudin as a Measure of Thrombin Activity at, or within, the Rabbit Aorta Wall In Vitro and In Vivo

Thrombosis and Haemostasis ◽

10.1055/s-0038-1642467 ◽

1994 ◽

Vol 71 (04) ◽

pp. 499-506 ◽

Cited By ~ 10

Author(s):

Mark W C Hatton ◽

Bonnie Ross-Ouellet

Keyword(s):

Rabbit Aorta ◽

Balloon Injury ◽

Recombinant Hirudin ◽

Aorta Wall ◽

Thrombin Activity ◽

Before And After ◽

The Matrix

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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Targeting Platelets Containing Electro-encapsulated lloprost to Balloon Injured Aorta in Rats

Thrombosis and Haemostasis ◽

10.1055/s-0038-1653809 ◽

1995 ◽

Vol 73 (03) ◽

pp. 535-542 ◽

Cited By ~ 1

Author(s):

N Crawford ◽

A Chajara ◽

G Pfliegler ◽

B EI Gamal ◽

L Brewer ◽

...

Keyword(s):

Time Course ◽

Therapeutic Potential ◽

Simple Procedure ◽

Rat Aorta ◽

Balloon Injury ◽

Post Injury ◽

Antiproliferative Effects ◽

Platelet Deposition ◽

Total Dna ◽

Novel Drug

SummaryDrugs can be electro-encapsulated within platelets and targeted to damaged blood vessels by exploiting the platelet’s natural haemostatic properties to adhere to collagen and other vessel wall constituents revealed by injury. A rat aorta balloon angioplasty model has been used to study the effect on platelet deposition of giving iloprost loaded platelets i.v. during the balloon injury. After labelling the circulating platelets with 111-Indium before balloon injury, time course studies showed maximum platelet deposition on the injured aorta occurred at about 1 h post-injury and the deposition remained stable over the next 2-3 h. When iloprost-loaded platelets were given i.v. during injury and the circulating platelet pool labelled with 111-Indium 30 min later, platelet deposition, measured at 2 h postinjury, was substantially and significantly reduced compared with control platelet treatment. Some antiproliferative effects of iloprost-loaded platelets given i.v. during injury have also been observed. Whereas the incorporation of [3H]-thymidine into aorta intima-media DNA at 3 days post injury was 62-fold higher in balloon injured rats than in control sham operated rats, thymidine incorporation into intima/media of rats which had received iloprost loaded platelets during injury was reduced as compared with rats subjected only to the injury procedure. The reduction was only of near significance, however, but at 14 days after injury the total DNA content of the aorta intima/media of rats given iloprost loaded platelets during injury was significantly reduced. Although iloprost loaded platelets can clearly inhibit excessive platelet deposition, other encapsulated agents may have greater anti-proliferative effects. These studies have shown that drug loaded platelets can be targeted to injured arteries, where they may be retained as depots for local release. We believe this novel drug delivery protocol may have therapeutic potential in reducing the incidence of occlusion and restenosis after angioplasty and thrombolysis treatment. Electro-encapsulation of drugs into platelets is a simple procedure and, using autologous and fully biocompatible and biodegradable platelets as delivery vehicles, might overcome some of the immunological and toxicological problems which have been encountered with other delivery vectors such as liposomes, microbeads, synthetic microcapsules and antibodies.

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