Local overexpression of monocyte chemoattractant protein-1 at vessel wall induces infiltration of macrophages and formation of atherosclerotic lesion

Synergism with hypercholesterolemia

Masayuki Namiki, Seinosuke Kawashima, Tomoya Yamashita, Masanori Ozaki, Tetsuaki Hirase, Tatsuro Ishida, Nobutaka Inoue, Ken Ichi Hirata, Akihiro Matsukawa, Ryuichi Morishita, Yasufumi Kaneda, Mitsuhiro Yokoyama

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

Monocyte/macrophage infiltration to the arterial wall is an initial step in atherosclerosis, and monocyte chemoattractant protein-1 (MCP-1) is thought to play a central role in the recruitment of these cells. In the present study, we examined the role of local expression of MCP-1 at the vessel wall in the initiation and development of atherosclerosis. We transfected the cDNA encoding rat MCP-1 into the vessel wall of the rabbit carotid artery with the use of the hemagglutinating virus of Japan (HVJ)-liposome method. The rabbits were divided into the following groups: (1) those fed normal chow and transfected with MCP-1-HVJ, (2) those fed a high cholesterol diet (1% cholesterol) and transfected with MCP-1-HVJ, and (3) those fed a high cholesterol diet and transfected with control-HVJ. Prescribed diets were started 2 weeks before transfection and were continued for another 2 weeks. In group 1, vascular lesion formation was not found, and anti-rabbit monocyte/macrophage antibody (RAM-11) staining for monocytes/macrophages was negative, although anti-rat MCP-1 antibody (R-17) staining for rat MCP-1 was positive mainly in endothelial cells. Cholesterol feeding increased plasma cholesterol levels to 1801±444 mg/dL in group 2. In group 2, all rabbits displayed neointimal formation with infiltration of RAM-11-positive cells, and a part of the lesion was also positive for Sudan III lipid staining. In group 3, hypercholesterolemia did not induce the infiltration of monocytes/macrophages and subsequent lesion formation in the vessel wall despite definite upregulation of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 on the endothelium. To initiate atherosclerotic changes, local MCP-1 overexpression at the vessel is not sufficient, and activation of other factors induced by hypercholesterolemia is required.

Original languageEnglish
Pages (from-to)115-120
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume22
Issue number1
DOIs
Publication statusPublished - 2002
Externally publishedYes

Fingerprint

Chemokine CCL2
Sendai virus
Hypercholesterolemia
Macrophages
Cholesterol
Monocytes
Rabbits
sudan III
Staining and Labeling
Diet
Atherosclerosis
Vascular Cell Adhesion Molecule-1
Antibodies
Intercellular Adhesion Molecule-1
Carotid Arteries
Liposomes
Endothelium
Transfection
Blood Vessels
Up-Regulation

Keywords

  • Atherosclerosis
  • Hypercholesterolemia
  • Monocyte chemoattractant protein-1

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Local overexpression of monocyte chemoattractant protein-1 at vessel wall induces infiltration of macrophages and formation of atherosclerotic lesion : Synergism with hypercholesterolemia. / Namiki, Masayuki; Kawashima, Seinosuke; Yamashita, Tomoya; Ozaki, Masanori; Hirase, Tetsuaki; Ishida, Tatsuro; Inoue, Nobutaka; Hirata, Ken Ichi; Matsukawa, Akihiro; Morishita, Ryuichi; Kaneda, Yasufumi; Yokoyama, Mitsuhiro.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 22, No. 1, 2002, p. 115-120.

Research output: Contribution to journalArticle

Namiki, Masayuki ; Kawashima, Seinosuke ; Yamashita, Tomoya ; Ozaki, Masanori ; Hirase, Tetsuaki ; Ishida, Tatsuro ; Inoue, Nobutaka ; Hirata, Ken Ichi ; Matsukawa, Akihiro ; Morishita, Ryuichi ; Kaneda, Yasufumi ; Yokoyama, Mitsuhiro. / Local overexpression of monocyte chemoattractant protein-1 at vessel wall induces infiltration of macrophages and formation of atherosclerotic lesion : Synergism with hypercholesterolemia. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2002 ; Vol. 22, No. 1. pp. 115-120.
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AU - Yamashita, Tomoya

AU - Ozaki, Masanori

AU - Hirase, Tetsuaki

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