PMID- 11788470 OWN - NLM STAT- MEDLINE DCOM- 20020207 LR - 20190901 IS - 1524-4636 (Electronic) IS - 1079-5642 (Linking) VI - 22 IP - 1 DP - 2002 Jan TI - Local overexpression of monocyte chemoattractant protein-1 at vessel wall induces infiltration of macrophages and formation of atherosclerotic lesion: synergism with hypercholesterolemia. PG - 115-20 AB - 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. FAU - Namiki, Masayuki AU - Namiki M AD - Division of Cardiovascular and Respiratory Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. FAU - Kawashima, Seinosuke AU - Kawashima S FAU - Yamashita, Tomoya AU - Yamashita T FAU - Ozaki, Masanori AU - Ozaki M FAU - Hirase, Tetsuaki AU - Hirase T FAU - Ishida, Tatsuro AU - Ishida T FAU - Inoue, Nobutaka AU - Inoue N FAU - Hirata, Ken-ichi AU - Hirata K FAU - Matsukawa, Akihiro AU - Matsukawa A FAU - Morishita, Ryuichi AU - Morishita R FAU - Kaneda, Yasufumi AU - Kaneda Y FAU - Yokoyama, Mitsuhiro AU - Yokoyama M LA - eng PT - Journal Article PL - United States TA - Arterioscler Thromb Vasc Biol JT - Arteriosclerosis, thrombosis, and vascular biology JID - 9505803 RN - 0 (Antibodies, Monoclonal) RN - 0 (Chemokine CCL2) RN - 0 (Vascular Cell Adhesion Molecule-1) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Animals MH - Antibodies, Monoclonal MH - Arteriosclerosis/blood/etiology/*pathology MH - Carotid Artery Diseases/etiology MH - Cell Movement/*physiology MH - Chemokine CCL2/genetics/*metabolism MH - Cholesterol/administration & dosage/blood MH - Diet, Atherogenic MH - Endothelium, Vascular/*pathology MH - Hypercholesterolemia/complications MH - Intercellular Adhesion Molecule-1/genetics/metabolism MH - Macrophages/*physiology MH - Male MH - Monocytes/*physiology MH - Rabbits MH - Rats MH - Transfection MH - Up-Regulation MH - Vascular Cell Adhesion Molecule-1/genetics/metabolism EDAT- 2002/01/15 10:00 MHDA- 2002/02/08 10:01 CRDT- 2002/01/15 10:00 PHST- 2002/01/15 10:00 [pubmed] PHST- 2002/02/08 10:01 [medline] PHST- 2002/01/15 10:00 [entrez] AID - 10.1161/hq0102.102278 [doi] PST - ppublish SO - Arterioscler Thromb Vasc Biol. 2002 Jan;22(1):115-20. doi: 10.1161/hq0102.102278.