Local Delivery of a Tissue Factor Antibody Reduces Early Leukocyte Infiltration but Fails to Limit Intimal Hyperplasia in Experimental Vein Grafts1

Purpose: To investigate the development of intimal hyperplasia in response to percutaneous transluminal coronary angioplasty (PTCA) followed by local delivery of the nitric oxide (NO) donor 3-morpholino-sydnonimine (SIN-1). Material and Methods: Overdilation PTCA was performed in coronary arteries in 20 healthy pigs. One of the dilated segments was additionally treated with local delivery of SIN-1 for 10 min. Segments distal to the treated part of the arteries served as controls. Arteries were radiographically depicted and analyzed after 1 and 8 weeks for actin, myosin and intermediate filaments (IF), nitric oxide synthetase (NOS) and histological evaluation. Results: Segments treated with PTCA+SIN-1 showed a significantly ( p = 0.03) larger luminal diameter compared with PTCA only treated segments. The luminal loss after SIN-1 was not significant compared with the diameter prior to treatment. Endothelial NOS content was significantly lower in the PTCA+SIN-1 group compared with the PTCA group after 1 ( p = 0.03) and 8 weeks ( p = 0.013). IF/actin ratio after 1 week was significantly increased in PTCA-treated segments compared with untreated controls ( p = 0.004), and compared with PTCA+SIN-1-treated segments ( p = 0.004). Conclusion: PTCA-induced intimal hyperplasia was potently inhibited by local delivery of the NO donor SIN-1. Momentary events at the time of injury play a significant role in the development of intimal hyperplasia and long-lasting down-regulation of the endothelial NOS expression after SIN-1 exposure is suggested. The IF/actin ratio can be useful as an early marker of intimal hyperplasia.

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Inhibition of intimal hyperplasia via local delivery of vascular endothelial growth factor cDNA nanoparticles in a rabbit model of restenosis induced by abdominal aorta balloon injury

Experimental and Therapeutic Medicine ◽

10.3892/etm.2015.2438 ◽

2015 ◽

Vol 10 (1) ◽

pp. 55-61 ◽

Cited By ~ 2

Author(s):

HONGZHI XIE ◽

JING YANG ◽

YECHEN HAN ◽

XUEQING ZHU ◽

QUAN FANG

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Abdominal Aorta ◽

Intimal Hyperplasia ◽

Rabbit Model ◽

Local Delivery ◽

Vascular Endothelial ◽

Balloon Injury ◽

Endothelial Growth Factor

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Local delivery of halofuginone ameliorates restenosis by inducing adaptive remodeling, reducing intimal hyperplasia, and preserving re-endothelialization

Journal of the American College of Surgeons ◽

10.1016/j.jamcollsurg.2013.07.370 ◽

2013 ◽

Vol 217 (3) ◽

pp. S157

Author(s):

Shakti A. Goel ◽

Lian-Wang Guo ◽

Toshio Takayama ◽

Christopher Little ◽

Drew A. Roenneburg ◽

...

Keyword(s):

Intimal Hyperplasia ◽

Local Delivery

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Local delivery of E2F decoy oligodeoxynucleotides using ultrasound with microbubble agent (Optison) inhibits intimal hyperplasia after balloon injury in rat carotid artery model

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2004.03.070 ◽

2004 ◽

Vol 317 (2) ◽

pp. 508-514 ◽

Cited By ~ 52

Author(s):

Naotaka Hashiya ◽

Motokuni Aoki ◽

Katsuro Tachibana ◽

Yoshiaki Taniyama ◽

Keita Yamasaki ◽

...

Keyword(s):

Carotid Artery ◽

Intimal Hyperplasia ◽

Local Delivery ◽

Balloon Injury ◽

Microbubble Agent

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Mice deficient in tissue factor demonstrate attenuated intimal hyperplasia in response to vascular injury and decreased smooth muscle cell migration

Thrombosis and Haemostasis ◽

10.1160/th04-02-0122 ◽

2004 ◽

Vol 92 (09) ◽

pp. 451-458 ◽

Cited By ~ 30

Author(s):

Robert Pyo ◽

Yuichiro Sato ◽

Nigel Mackman ◽

Mark Taubman

Keyword(s):

Smooth Muscle ◽

Cell Migration ◽

Smooth Muscle Cell ◽

Tissue Factor ◽

Muscle Cell ◽

Vascular Injury ◽

Intimal Hyperplasia ◽

Coagulation Cascade ◽

Genetically Engineered Mice ◽

Smooth Muscle Cell Migration

SummaryTissue factor (TF) is the primary initiator of the coagulation cascade and is thought to play a key role in the generation of arterial thrombosis. Recent studies have suggested that TF mediates inflammatory processes in the arterial wall and may be an important regulator of intimal hyperplasia. We have employed genetically engineered mice (mTF−/−/hTF+) with markedly diminished TF activity (≈1% normal levels) to examine the role of TF in mediating the response to arterial injury. mTF−/−/hTF+ displayed a marked reduction in intimal hyperplasia (46% decrease in intimal area, 60% decrease in intimal/medial ratio) in response to femoral artery injury when compared to wild type controls. The decreased intimal hyperplasia seen in low TF mice was noted in a model of vascular injury not associated with significant thrombosis, suggesting that it may be mediated by non-procoagulant properties of TF. Smooth muscle cells from mTF−/−/hTF+ mice grew normally in response to serum, but exhibited a marked defect in cell migration in a modified Boyden chamber assay. In contrast, there was no difference in platelet derived growth factorinduced migration, suggesting that the effect of TF on smooth muscle cell migration is agonist dependent. These data suggest that TF may mediate intimal hyperplasia by regulating smooth muscle cell migration.

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