Thalidomide as a Potent Inhibitor of Neointimal Hyperplasia after Balloon Injury in Rat Carotid Artery

Seung Jung Park, Hyo Soo Kim, Han Mo Yang, Kyung Woo Park, Seock Won Youn, Soo In Jeon, Dae Hee Kim, Bon Kwon Koo, In Ho Chae, Dong Joo Choi, Byung Hee Oh, Myoung Mook Lee, Young Bae Park

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Objective-Inflammation is one of the main pathogeneses of neointimal hyperplasia after coronary intervention. Thalidomide, because of its potent antiinflammatory and immunomodulatory properties, is being re-evaluated in several clinical fields. Therefore, we examined whether thalidomide therapy affects neointimal formation. Methods and Results-In male Sprague-Dawley rats, 100 mg/kg of either thalidomide or sucrose (control) was administered daily from 3 days before injury to 2 weeks after conventional carotid artery denudation injury. Thalidomide administration resulted in a significant reduction of neointimal formation (neointima to media ratio 1.26±0.29 versus 0.35±0.13, P<0.001) and proliferative activity of vascular smooth muscle cells. In addition, arterial macrophage infiltration and local expressions of tumor necrosis factor alpha (TNF-α) and basic fibroblast growth factor (bFGF) in the injured arteries as measured by immunohistochemistry and immunoblot analysis were significantly reduced by thalidomide treatment. Serum TNF-α, measured by ELISA, was also significantly reduced in the thalidomide-treated animals compared with controls after injury (856±213 versus 449±68 pg/mL on day 3, P=0.001; 129±34 versus 63±18 pg/mL on day 14, P=0.001), and we observed a good positive correlation between the serum TNF-α levels and the severity of neointimal growth. Conclusions-We found that thalidomide, through its antiinflammatory and antiproliferative effects, significantly inhibits neointimal hyperplasia in balloon-injured rat carotid arteries. Our results suggest a potential role of thalidomide as a potent inhibitor of neointimal formation after angioplasty.

Original languageEnglish (US)
Pages (from-to)885-891
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume24
Issue number5
DOIs
StatePublished - May 1 2004

Fingerprint

Thalidomide
Carotid Arteries
Hyperplasia
Wounds and Injuries
Tumor Necrosis Factor-alpha
Anti-Inflammatory Agents
Carotid Artery Injuries
Neointima
Fibroblast Growth Factor 2
Serum
Vascular Smooth Muscle
Angioplasty
Smooth Muscle Myocytes
Sprague Dawley Rats
Sucrose
Arteries
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry
Macrophages
Inflammation

Keywords

  • BFGF
  • Inflammation
  • Neointima
  • Thalidomide
  • TNF-α

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Thalidomide as a Potent Inhibitor of Neointimal Hyperplasia after Balloon Injury in Rat Carotid Artery. / Park, Seung Jung; Kim, Hyo Soo; Yang, Han Mo; Park, Kyung Woo; Youn, Seock Won; Jeon, Soo In; Kim, Dae Hee; Koo, Bon Kwon; Chae, In Ho; Choi, Dong Joo; Oh, Byung Hee; Lee, Myoung Mook; Park, Young Bae.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 24, No. 5, 01.05.2004, p. 885-891.

Research output: Contribution to journalArticle

Park, SJ, Kim, HS, Yang, HM, Park, KW, Youn, SW, Jeon, SI, Kim, DH, Koo, BK, Chae, IH, Choi, DJ, Oh, BH, Lee, MM & Park, YB 2004, 'Thalidomide as a Potent Inhibitor of Neointimal Hyperplasia after Balloon Injury in Rat Carotid Artery', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 24, no. 5, pp. 885-891. https://doi.org/10.1161/01.ATV.0000124924.21961.c3
Park, Seung Jung ; Kim, Hyo Soo ; Yang, Han Mo ; Park, Kyung Woo ; Youn, Seock Won ; Jeon, Soo In ; Kim, Dae Hee ; Koo, Bon Kwon ; Chae, In Ho ; Choi, Dong Joo ; Oh, Byung Hee ; Lee, Myoung Mook ; Park, Young Bae. / Thalidomide as a Potent Inhibitor of Neointimal Hyperplasia after Balloon Injury in Rat Carotid Artery. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2004 ; Vol. 24, No. 5. pp. 885-891.
@article{d91b065eaf254f7bbd90fbb1a04e46df,
title = "Thalidomide as a Potent Inhibitor of Neointimal Hyperplasia after Balloon Injury in Rat Carotid Artery",
abstract = "Objective-Inflammation is one of the main pathogeneses of neointimal hyperplasia after coronary intervention. Thalidomide, because of its potent antiinflammatory and immunomodulatory properties, is being re-evaluated in several clinical fields. Therefore, we examined whether thalidomide therapy affects neointimal formation. Methods and Results-In male Sprague-Dawley rats, 100 mg/kg of either thalidomide or sucrose (control) was administered daily from 3 days before injury to 2 weeks after conventional carotid artery denudation injury. Thalidomide administration resulted in a significant reduction of neointimal formation (neointima to media ratio 1.26±0.29 versus 0.35±0.13, P<0.001) and proliferative activity of vascular smooth muscle cells. In addition, arterial macrophage infiltration and local expressions of tumor necrosis factor alpha (TNF-α) and basic fibroblast growth factor (bFGF) in the injured arteries as measured by immunohistochemistry and immunoblot analysis were significantly reduced by thalidomide treatment. Serum TNF-α, measured by ELISA, was also significantly reduced in the thalidomide-treated animals compared with controls after injury (856±213 versus 449±68 pg/mL on day 3, P=0.001; 129±34 versus 63±18 pg/mL on day 14, P=0.001), and we observed a good positive correlation between the serum TNF-α levels and the severity of neointimal growth. Conclusions-We found that thalidomide, through its antiinflammatory and antiproliferative effects, significantly inhibits neointimal hyperplasia in balloon-injured rat carotid arteries. Our results suggest a potential role of thalidomide as a potent inhibitor of neointimal formation after angioplasty.",
keywords = "BFGF, Inflammation, Neointima, Thalidomide, TNF-α",
author = "Park, {Seung Jung} and Kim, {Hyo Soo} and Yang, {Han Mo} and Park, {Kyung Woo} and Youn, {Seock Won} and Jeon, {Soo In} and Kim, {Dae Hee} and Koo, {Bon Kwon} and Chae, {In Ho} and Choi, {Dong Joo} and Oh, {Byung Hee} and Lee, {Myoung Mook} and Park, {Young Bae}",
year = "2004",
month = "5",
day = "1",
doi = "10.1161/01.ATV.0000124924.21961.c3",
language = "English (US)",
volume = "24",
pages = "885--891",
journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",
issn = "1079-5642",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Thalidomide as a Potent Inhibitor of Neointimal Hyperplasia after Balloon Injury in Rat Carotid Artery

AU - Park, Seung Jung

AU - Kim, Hyo Soo

AU - Yang, Han Mo

AU - Park, Kyung Woo

AU - Youn, Seock Won

AU - Jeon, Soo In

AU - Kim, Dae Hee

AU - Koo, Bon Kwon

AU - Chae, In Ho

AU - Choi, Dong Joo

AU - Oh, Byung Hee

AU - Lee, Myoung Mook

AU - Park, Young Bae

PY - 2004/5/1

Y1 - 2004/5/1

N2 - Objective-Inflammation is one of the main pathogeneses of neointimal hyperplasia after coronary intervention. Thalidomide, because of its potent antiinflammatory and immunomodulatory properties, is being re-evaluated in several clinical fields. Therefore, we examined whether thalidomide therapy affects neointimal formation. Methods and Results-In male Sprague-Dawley rats, 100 mg/kg of either thalidomide or sucrose (control) was administered daily from 3 days before injury to 2 weeks after conventional carotid artery denudation injury. Thalidomide administration resulted in a significant reduction of neointimal formation (neointima to media ratio 1.26±0.29 versus 0.35±0.13, P<0.001) and proliferative activity of vascular smooth muscle cells. In addition, arterial macrophage infiltration and local expressions of tumor necrosis factor alpha (TNF-α) and basic fibroblast growth factor (bFGF) in the injured arteries as measured by immunohistochemistry and immunoblot analysis were significantly reduced by thalidomide treatment. Serum TNF-α, measured by ELISA, was also significantly reduced in the thalidomide-treated animals compared with controls after injury (856±213 versus 449±68 pg/mL on day 3, P=0.001; 129±34 versus 63±18 pg/mL on day 14, P=0.001), and we observed a good positive correlation between the serum TNF-α levels and the severity of neointimal growth. Conclusions-We found that thalidomide, through its antiinflammatory and antiproliferative effects, significantly inhibits neointimal hyperplasia in balloon-injured rat carotid arteries. Our results suggest a potential role of thalidomide as a potent inhibitor of neointimal formation after angioplasty.

AB - Objective-Inflammation is one of the main pathogeneses of neointimal hyperplasia after coronary intervention. Thalidomide, because of its potent antiinflammatory and immunomodulatory properties, is being re-evaluated in several clinical fields. Therefore, we examined whether thalidomide therapy affects neointimal formation. Methods and Results-In male Sprague-Dawley rats, 100 mg/kg of either thalidomide or sucrose (control) was administered daily from 3 days before injury to 2 weeks after conventional carotid artery denudation injury. Thalidomide administration resulted in a significant reduction of neointimal formation (neointima to media ratio 1.26±0.29 versus 0.35±0.13, P<0.001) and proliferative activity of vascular smooth muscle cells. In addition, arterial macrophage infiltration and local expressions of tumor necrosis factor alpha (TNF-α) and basic fibroblast growth factor (bFGF) in the injured arteries as measured by immunohistochemistry and immunoblot analysis were significantly reduced by thalidomide treatment. Serum TNF-α, measured by ELISA, was also significantly reduced in the thalidomide-treated animals compared with controls after injury (856±213 versus 449±68 pg/mL on day 3, P=0.001; 129±34 versus 63±18 pg/mL on day 14, P=0.001), and we observed a good positive correlation between the serum TNF-α levels and the severity of neointimal growth. Conclusions-We found that thalidomide, through its antiinflammatory and antiproliferative effects, significantly inhibits neointimal hyperplasia in balloon-injured rat carotid arteries. Our results suggest a potential role of thalidomide as a potent inhibitor of neointimal formation after angioplasty.

KW - BFGF

KW - Inflammation

KW - Neointima

KW - Thalidomide

KW - TNF-α

UR - http://www.scopus.com/inward/record.url?scp=2442588852&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2442588852&partnerID=8YFLogxK

U2 - 10.1161/01.ATV.0000124924.21961.c3

DO - 10.1161/01.ATV.0000124924.21961.c3

M3 - Article

VL - 24

SP - 885

EP - 891

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

SN - 1079-5642

IS - 5

ER -