Abstract | BACKGROUND: METHODS: RESULTS:
Midkine expression reached the maximum level within 7 days after stenting and was detected in infiltrating macrophages. Differentiation of THP-1 cells to macrophage-like cells did not trigger midkine expression. Neither low-density lipoprotein nor oxidized low-density lipoprotein enhanced midkine expression in peritoneal macrophages that had been activated by thioglycollate, although these cells expressed a significant amount of midkine. CONCLUSION: The results indicate that macrophages are the major source of midkine in the atherosclerotic neointima. The amount of midkine expressed in macrophages may be sufficient (ie, further enhancement of the expression is not necessary) for the pathogenesis, because oxidized low-density lipoprotein stimulation did not induce the midkine expression. CLINICAL RELEVANCE: The growth factor midkine is induced during vascular stenosis in mouse and rat models with normal diet. Knockdown of midkine expression suppresses neointimal hyperplasia. The vascular response after stenting differs from that after balloon injury in that the inflammation is more prolonged and the accumulation of macrophages is more abundant in stent-injured vessel. We found here that macrophages are the major source of midkine in the atherosclerotic neointima of in- stent restenosis in hypercholesterolemic rabbits. Our data suggest that midkine has an important role in in- stent restenosis of atherosclerotic vessels and is a candidate molecular target to prevent in- stent restenosis.
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Authors | Hiroshi Narita, Sen Chen, Kimihiro Komori, Kenji Kadomatsu |
Journal | Journal of vascular surgery
(J Vasc Surg)
Vol. 47
Issue 6
Pg. 1322-9
(Jun 2008)
ISSN: 0741-5214 [Print] United States |
PMID | 18353604
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cholesterol, Dietary
- Cytokines
- Lipoproteins, LDL
- Metals
- oxidized low density lipoprotein
- Midkine
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Topics |
- Angioplasty, Balloon
(instrumentation)
- Animals
- Atherosclerosis
(etiology, immunology, metabolism, pathology, therapy)
- Cell Differentiation
- Cell Line
- Cell Movement
- Cells, Cultured
- Cholesterol, Dietary
(administration & dosage)
- Constriction, Pathologic
- Cytokines
(metabolism)
- Disease Models, Animal
- Humans
- Hypercholesterolemia
(complications, etiology, immunology, metabolism, pathology)
- Hyperplasia
- Iliac Artery
(immunology, metabolism, pathology)
- Lipoproteins, LDL
(metabolism)
- Macrophages
(immunology, metabolism)
- Male
- Metals
- Mice
- Midkine
- Prosthesis Design
- Rabbits
- Stents
- Time Factors
- Up-Regulation
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