Local overexpression of thrombomodulin for in vivo prevention of arterial thrombosis in a rabbit model

M. D. Kuo, J. M. Waugh, J. Li, E. Yuksel, M. Kattash, Romil Saxena, S. N. Thung, S. M. Shenaq, S. L C Woo

Research output: Contribution to journalArticle

Abstract

Endothelial thrombomodulin plays a critical role in hemostasis by binding thrombin and subsequently converting protein C to its active form-a powerful anticoagulant. Thrombomodulin thus represents a central mechanism by which patency is maintained in normal vessels. However, thrombomodulin expression decreases in perturbed endothelial cells, predisposing to thrombotic occlusion. Thus, an adenoviral construct expressing thrombomodulin was created and functionally characterized in vitro and in vivo. The impact of local overexprcssion of thrombomodulin on in vivo thrombus formation was subsequently examined in a stasis/injury model of arterial thrombosis. The construct prevented arterial thrombosis formation in all animals, while viral and nonviral controls typically developed occluding thrombi (p<0.01 vs viral and nonviral controls); overall mean cross sectional percent thrombus was 4.70+/ -1.07 for thrombomodulin treatments, while nonviral controls were 71.62+/ -5.70 and viral controls were 89.1 +/-3.43. No significant alterations in degree of overall inflammation or intima to media ratio were observed in the thrombomodulin group relative to controls. This construct thus offers a viable technique for promoting a locally thromboresistant small caliber artery, without the inflammatory damage that has limited many other adenoviral applications.

Original languageEnglish
JournalFASEB Journal
Volume12
Issue number5
StatePublished - Mar 20 1998
Externally publishedYes

Fingerprint

Thrombomodulin
thrombosis
Thrombosis
rabbits
Rabbits
hemostasis
anticoagulants
thrombin
arteries
endothelial cells
inflammation
animals
proteins
Endothelial cells
Protein C
Hemostasis
Thrombin
Anticoagulants
methodology
Animals

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Kuo, M. D., Waugh, J. M., Li, J., Yuksel, E., Kattash, M., Saxena, R., ... Woo, S. L. C. (1998). Local overexpression of thrombomodulin for in vivo prevention of arterial thrombosis in a rabbit model. FASEB Journal, 12(5).

Local overexpression of thrombomodulin for in vivo prevention of arterial thrombosis in a rabbit model. / Kuo, M. D.; Waugh, J. M.; Li, J.; Yuksel, E.; Kattash, M.; Saxena, Romil; Thung, S. N.; Shenaq, S. M.; Woo, S. L C.

In: FASEB Journal, Vol. 12, No. 5, 20.03.1998.

Research output: Contribution to journalArticle

Kuo, MD, Waugh, JM, Li, J, Yuksel, E, Kattash, M, Saxena, R, Thung, SN, Shenaq, SM & Woo, SLC 1998, 'Local overexpression of thrombomodulin for in vivo prevention of arterial thrombosis in a rabbit model', FASEB Journal, vol. 12, no. 5.
Kuo, M. D. ; Waugh, J. M. ; Li, J. ; Yuksel, E. ; Kattash, M. ; Saxena, Romil ; Thung, S. N. ; Shenaq, S. M. ; Woo, S. L C. / Local overexpression of thrombomodulin for in vivo prevention of arterial thrombosis in a rabbit model. In: FASEB Journal. 1998 ; Vol. 12, No. 5.
@article{27a646cf5a544e89b5dca24b09378187,
title = "Local overexpression of thrombomodulin for in vivo prevention of arterial thrombosis in a rabbit model",
abstract = "Endothelial thrombomodulin plays a critical role in hemostasis by binding thrombin and subsequently converting protein C to its active form-a powerful anticoagulant. Thrombomodulin thus represents a central mechanism by which patency is maintained in normal vessels. However, thrombomodulin expression decreases in perturbed endothelial cells, predisposing to thrombotic occlusion. Thus, an adenoviral construct expressing thrombomodulin was created and functionally characterized in vitro and in vivo. The impact of local overexprcssion of thrombomodulin on in vivo thrombus formation was subsequently examined in a stasis/injury model of arterial thrombosis. The construct prevented arterial thrombosis formation in all animals, while viral and nonviral controls typically developed occluding thrombi (p<0.01 vs viral and nonviral controls); overall mean cross sectional percent thrombus was 4.70+/ -1.07 for thrombomodulin treatments, while nonviral controls were 71.62+/ -5.70 and viral controls were 89.1 +/-3.43. No significant alterations in degree of overall inflammation or intima to media ratio were observed in the thrombomodulin group relative to controls. This construct thus offers a viable technique for promoting a locally thromboresistant small caliber artery, without the inflammatory damage that has limited many other adenoviral applications.",
author = "Kuo, {M. D.} and Waugh, {J. M.} and J. Li and E. Yuksel and M. Kattash and Romil Saxena and Thung, {S. N.} and Shenaq, {S. M.} and Woo, {S. L C}",
year = "1998",
month = "3",
day = "20",
language = "English",
volume = "12",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "5",

}

TY - JOUR

T1 - Local overexpression of thrombomodulin for in vivo prevention of arterial thrombosis in a rabbit model

AU - Kuo, M. D.

AU - Waugh, J. M.

AU - Li, J.

AU - Yuksel, E.

AU - Kattash, M.

AU - Saxena, Romil

AU - Thung, S. N.

AU - Shenaq, S. M.

AU - Woo, S. L C

PY - 1998/3/20

Y1 - 1998/3/20

N2 - Endothelial thrombomodulin plays a critical role in hemostasis by binding thrombin and subsequently converting protein C to its active form-a powerful anticoagulant. Thrombomodulin thus represents a central mechanism by which patency is maintained in normal vessels. However, thrombomodulin expression decreases in perturbed endothelial cells, predisposing to thrombotic occlusion. Thus, an adenoviral construct expressing thrombomodulin was created and functionally characterized in vitro and in vivo. The impact of local overexprcssion of thrombomodulin on in vivo thrombus formation was subsequently examined in a stasis/injury model of arterial thrombosis. The construct prevented arterial thrombosis formation in all animals, while viral and nonviral controls typically developed occluding thrombi (p<0.01 vs viral and nonviral controls); overall mean cross sectional percent thrombus was 4.70+/ -1.07 for thrombomodulin treatments, while nonviral controls were 71.62+/ -5.70 and viral controls were 89.1 +/-3.43. No significant alterations in degree of overall inflammation or intima to media ratio were observed in the thrombomodulin group relative to controls. This construct thus offers a viable technique for promoting a locally thromboresistant small caliber artery, without the inflammatory damage that has limited many other adenoviral applications.

AB - Endothelial thrombomodulin plays a critical role in hemostasis by binding thrombin and subsequently converting protein C to its active form-a powerful anticoagulant. Thrombomodulin thus represents a central mechanism by which patency is maintained in normal vessels. However, thrombomodulin expression decreases in perturbed endothelial cells, predisposing to thrombotic occlusion. Thus, an adenoviral construct expressing thrombomodulin was created and functionally characterized in vitro and in vivo. The impact of local overexprcssion of thrombomodulin on in vivo thrombus formation was subsequently examined in a stasis/injury model of arterial thrombosis. The construct prevented arterial thrombosis formation in all animals, while viral and nonviral controls typically developed occluding thrombi (p<0.01 vs viral and nonviral controls); overall mean cross sectional percent thrombus was 4.70+/ -1.07 for thrombomodulin treatments, while nonviral controls were 71.62+/ -5.70 and viral controls were 89.1 +/-3.43. No significant alterations in degree of overall inflammation or intima to media ratio were observed in the thrombomodulin group relative to controls. This construct thus offers a viable technique for promoting a locally thromboresistant small caliber artery, without the inflammatory damage that has limited many other adenoviral applications.

UR - http://www.scopus.com/inward/record.url?scp=33749311776&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33749311776&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:33749311776

VL - 12

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 5

ER -