Antimonocyte chemoattractant protein-1 gene therapy attenuates graft vasculopathy

Akio Saiura, Masataka Sata, Ken Ichi Hiasa, Shiro Kitamoto, Miwa Washida, Kensuke Egashira, Ryozo Nagai, Masatoshi Makuuchi

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Objective - Accelerated coronary arteriosclerosis remains a major problem in the long-term survival of cardiac transplant recipients. However, the pathogenesis of graft vasculopathy is poorly understood, and there is no effective therapy. Transplant arteriosclerosis is characterized by early mononuclear cell attachment on the transplanted vessel followed by development of concentric neointimal hyperplasia. Early and persistent expression of monocyte chemoattractant protein-1 (MCP-1) in cardiac allografts has been implicated for the pathogenesis of transplant arteriosclerosis. Methods and Results - We investigated whether anti-MCP-1 gene therapy can inhibit the development of intima hyperplasia in a mouse model of cardiac transplantation. Either the dominant-negative form of MCP-1 (7ND) or control vector was transfected into the skeletal muscles of B10.D2 mice. Cardiac allografts from DBA/2 mice were transplanted heterotopically into B10.D2 mice. 7ND gene transfer was associated with a significant reduction of the number of mononuclear cells accumulating in the lumen of the graft coronary arteries at 1 week and an attenuation of the development of the lesion at 8 weeks (intima/media ratio 0.79±0.05 versus 0.48±0.04). Conclusions - The MCP-1/chemokine receptor 2 (CCR2) signaling pathway plays a critical role in the pathogenesis of graft vasculopathy. This new anti-MCP-1 gene therapy might be useful to treat graft vascular disease.

Original languageEnglish
Pages (from-to)1886-1890
Number of pages5
JournalArteriosclerosis, thrombosis, and vascular biology
Volume24
Issue number10
DOIs
Publication statusPublished - Oct 1 2004

Fingerprint

Chemotactic Factors
Genetic Therapy
Chemokine CCL2
Transplants
Proteins
Arteriosclerosis
Hyperplasia
Allografts
CCR2 Receptors
Inbred DBA Mouse
Chemokine Receptors
Heart Transplantation
Vascular Diseases
Coronary Artery Disease
Coronary Vessels
Skeletal Muscle
Cell Count
Survival
Genes

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Antimonocyte chemoattractant protein-1 gene therapy attenuates graft vasculopathy. / Saiura, Akio; Sata, Masataka; Hiasa, Ken Ichi; Kitamoto, Shiro; Washida, Miwa; Egashira, Kensuke; Nagai, Ryozo; Makuuchi, Masatoshi.

In: Arteriosclerosis, thrombosis, and vascular biology, Vol. 24, No. 10, 01.10.2004, p. 1886-1890.

Research output: Contribution to journalArticle

Saiura, Akio ; Sata, Masataka ; Hiasa, Ken Ichi ; Kitamoto, Shiro ; Washida, Miwa ; Egashira, Kensuke ; Nagai, Ryozo ; Makuuchi, Masatoshi. / Antimonocyte chemoattractant protein-1 gene therapy attenuates graft vasculopathy. In: Arteriosclerosis, thrombosis, and vascular biology. 2004 ; Vol. 24, No. 10. pp. 1886-1890.
@article{00e952dd7a874a7689dd44cef0dac241,
title = "Antimonocyte chemoattractant protein-1 gene therapy attenuates graft vasculopathy",
abstract = "Objective - Accelerated coronary arteriosclerosis remains a major problem in the long-term survival of cardiac transplant recipients. However, the pathogenesis of graft vasculopathy is poorly understood, and there is no effective therapy. Transplant arteriosclerosis is characterized by early mononuclear cell attachment on the transplanted vessel followed by development of concentric neointimal hyperplasia. Early and persistent expression of monocyte chemoattractant protein-1 (MCP-1) in cardiac allografts has been implicated for the pathogenesis of transplant arteriosclerosis. Methods and Results - We investigated whether anti-MCP-1 gene therapy can inhibit the development of intima hyperplasia in a mouse model of cardiac transplantation. Either the dominant-negative form of MCP-1 (7ND) or control vector was transfected into the skeletal muscles of B10.D2 mice. Cardiac allografts from DBA/2 mice were transplanted heterotopically into B10.D2 mice. 7ND gene transfer was associated with a significant reduction of the number of mononuclear cells accumulating in the lumen of the graft coronary arteries at 1 week and an attenuation of the development of the lesion at 8 weeks (intima/media ratio 0.79±0.05 versus 0.48±0.04). Conclusions - The MCP-1/chemokine receptor 2 (CCR2) signaling pathway plays a critical role in the pathogenesis of graft vasculopathy. This new anti-MCP-1 gene therapy might be useful to treat graft vascular disease.",
author = "Akio Saiura and Masataka Sata and Hiasa, {Ken Ichi} and Shiro Kitamoto and Miwa Washida and Kensuke Egashira and Ryozo Nagai and Masatoshi Makuuchi",
year = "2004",
month = "10",
day = "1",
doi = "10.1161/01.ATV.0000141045.49616.6f",
language = "English",
volume = "24",
pages = "1886--1890",
journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",
issn = "1079-5642",
publisher = "Lippincott Williams and Wilkins",
number = "10",

}

TY - JOUR

T1 - Antimonocyte chemoattractant protein-1 gene therapy attenuates graft vasculopathy

AU - Saiura, Akio

AU - Sata, Masataka

AU - Hiasa, Ken Ichi

AU - Kitamoto, Shiro

AU - Washida, Miwa

AU - Egashira, Kensuke

AU - Nagai, Ryozo

AU - Makuuchi, Masatoshi

PY - 2004/10/1

Y1 - 2004/10/1

N2 - Objective - Accelerated coronary arteriosclerosis remains a major problem in the long-term survival of cardiac transplant recipients. However, the pathogenesis of graft vasculopathy is poorly understood, and there is no effective therapy. Transplant arteriosclerosis is characterized by early mononuclear cell attachment on the transplanted vessel followed by development of concentric neointimal hyperplasia. Early and persistent expression of monocyte chemoattractant protein-1 (MCP-1) in cardiac allografts has been implicated for the pathogenesis of transplant arteriosclerosis. Methods and Results - We investigated whether anti-MCP-1 gene therapy can inhibit the development of intima hyperplasia in a mouse model of cardiac transplantation. Either the dominant-negative form of MCP-1 (7ND) or control vector was transfected into the skeletal muscles of B10.D2 mice. Cardiac allografts from DBA/2 mice were transplanted heterotopically into B10.D2 mice. 7ND gene transfer was associated with a significant reduction of the number of mononuclear cells accumulating in the lumen of the graft coronary arteries at 1 week and an attenuation of the development of the lesion at 8 weeks (intima/media ratio 0.79±0.05 versus 0.48±0.04). Conclusions - The MCP-1/chemokine receptor 2 (CCR2) signaling pathway plays a critical role in the pathogenesis of graft vasculopathy. This new anti-MCP-1 gene therapy might be useful to treat graft vascular disease.

AB - Objective - Accelerated coronary arteriosclerosis remains a major problem in the long-term survival of cardiac transplant recipients. However, the pathogenesis of graft vasculopathy is poorly understood, and there is no effective therapy. Transplant arteriosclerosis is characterized by early mononuclear cell attachment on the transplanted vessel followed by development of concentric neointimal hyperplasia. Early and persistent expression of monocyte chemoattractant protein-1 (MCP-1) in cardiac allografts has been implicated for the pathogenesis of transplant arteriosclerosis. Methods and Results - We investigated whether anti-MCP-1 gene therapy can inhibit the development of intima hyperplasia in a mouse model of cardiac transplantation. Either the dominant-negative form of MCP-1 (7ND) or control vector was transfected into the skeletal muscles of B10.D2 mice. Cardiac allografts from DBA/2 mice were transplanted heterotopically into B10.D2 mice. 7ND gene transfer was associated with a significant reduction of the number of mononuclear cells accumulating in the lumen of the graft coronary arteries at 1 week and an attenuation of the development of the lesion at 8 weeks (intima/media ratio 0.79±0.05 versus 0.48±0.04). Conclusions - The MCP-1/chemokine receptor 2 (CCR2) signaling pathway plays a critical role in the pathogenesis of graft vasculopathy. This new anti-MCP-1 gene therapy might be useful to treat graft vascular disease.

UR - http://www.scopus.com/inward/record.url?scp=5344251654&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=5344251654&partnerID=8YFLogxK

U2 - 10.1161/01.ATV.0000141045.49616.6f

DO - 10.1161/01.ATV.0000141045.49616.6f

M3 - Article

C2 - 15284091

AN - SCOPUS:5344251654

VL - 24

SP - 1886

EP - 1890

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

SN - 1079-5642

IS - 10

ER -