Title
Anti-MCP-1 gene therapy inhibits vascular smooth muscle cells proliferation and attenuates vein graft thickening both in vitro and in vivo
Author
Schepers, A.
Eefting, D.
Bonta, P.I.
Grimbergen, J.M.
de Vries, M.R.
van Weel, V.
de Vries, C.J.
Egashira, K.
van Bockel, J.H.
Quax, P.H.A.
TNO Kwaliteit van Leven
Publication year
2006
Abstract
OBJECTIVE - Because late vein graft failure is caused by intimal hyperplasia (IH) and accelerated atherosclerosis, and these processes are thought to be inflammation driven, influx of monocytes is one of the first phenomena seen in IH, we would like to provide direct evidence for a role of the MCP-1 pathway in the development of vein graft disease. METHODS AND RESULTS - MCP-1 expression is demonstrated in various stages of vein graft disease in a murine model in which venous interpositions are placed in the carotid arteries of hypercholesterolemic ApoE3Leiden mice and in cultured human saphenous vein (HSV) segments in which IH occurs. The functional involvement of MCP-1 in vein graft remodeling is demonstrated by blocking the MCP-1 receptor CCR-2 using 7ND-MCP-1. 7ND-MCP1 gene transfer resulted in 51% reduction in IH in the mouse model, when compared with controls. In HSV cultures neointima formation was inhibited by 53%. In addition, we demonstrate a direct inhibitory effect of 7ND-MCP-1 on the proliferation of smooth muscle cell (SMC) in HSV cultures and in SMC cell cultures. CONCLUSION - These data, for the first time, prove that MCP-1 has a pivotal role in vein graft thickening due to intimal hyperplasia and accelerated atherosclerosis. © 2006 American Heart Association, Inc. Chemicals / CAS: Ccl2 protein, mouse; Chemokine CCL2; monocyte chemoattractant protein 1 receptor, 156286-78-1; Receptors, Chemokine
Subject
Biology
Biomedical Research
Inflammation
Intimal hyperplasia
MCP-1
Smooth muscle cells
Vein graft disease
Apolipoprotein E
Chemokine receptor CCR2
Monocyte chemotactic protein 1
Animal experiment
Animal model
Animal tissue
Artery intima proliferation
Atherosclerosis
Carotid artery
Cell proliferation
Controlled study
Graft failure
Human
Human cell
Human tissue
Hypercholesterolemia
In vitro study
In vivo study
Monocyte
Mouse
Nonhuman
Protein expression
Saphenous vein
Vascular smooth muscle
Vein graft
Amino Acid Sequence
Animals
Carotid Arteries
Cell Proliferation
Cells, Cultured
Chemokine CCL2
Gene Therapy
Humans
Hypercholesterolemia
Male
Mice
Mice, Inbred C57BL
Muscle, Smooth, Vascular
Myocytes, Smooth Muscle
Organ Culture Techniques
Receptors, Chemokine
Saphenous Vein
Sequence Deletion
Tunica Intima
To reference this document use:
http://resolver.tudelft.nl/uuid:c4cd3e3d-24f3-41ad-90f9-f83a5eb1b2e4
DOI
https://doi.org/10.1161/01.atv.0000235694.69719.e2
TNO identifier
239462
ISSN
1079-5642
Source
Arteriosclerosis, Thrombosis, and Vascular Biology, 26 (9), 2063-2069
Document type
article