| Project/Area Number |
16590717
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | JUNTENDO UNIVERSITY |
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Principal Investigator |
KATOH Youichi Juntendo Univ., Dept of Cardiology, Assistant Prof., 医学部, 講師 (00231259)
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| Co-Investigator(Kenkyū-buntansha) |
SUGIMOTO Ko-ichi Juntendo Univ, Dept of Hematology, Associate Prof, 医学部, 助教授 (50281358)
YUHARA Chiharu Juntendo Univ., Dept of Gynedology, Attending Doctor, 医学部, 助手 (90281360)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | vascular smooth muscle cell / bone marrow stromal cell / PPAR-gamma / stem cell / progenitor cell / metabolic syndrome / atherosclerosis / neointimal hyperplasia / GFP / プロモーター / Growth Factor |
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| Research Abstract |
BACKGROUND : The metabolic syndrome is defined as a constellation of metabolic risk factors that are associated with coronary heart disease. Peroxisome proliferator-activated receptor-gamma (PPAR-γ) is an established therapeutic target in the treatment of the metabolic syndrome. However, it is unknown whether PPAR-γ agonists favorably modulate bone marrow (BM)-derived smooth muscle cells in atherosclerotic plaques. METHODS AND RESULTS : We investigated the effects of PPAR-γ agonist, pioglitazone, on BM-derived smooth muscle progenitor cells that may contribute to neointimal hyperplasia. After the transfection of the human SM22a promoter (-480 bp) /green fluorescent protein (GFP) construct, BM stromal cells were incubated with or without pioglitazone at 1 umol/L in the presence of PDGF-BB at 1.0 ng/ml as previously described (Kashiwakura, Katoh, et al. Circulation. 2003). Pioglitazone markedly suppressed GFP-positive colony formation to 12±5 %. Immunocytochemistry staining by SMC-specific antibodies recognizing a-SM actin, calponin, and SM-1 demonstrated that pioglitazone decreased the number of clones stained by them to 10±4 %. Western and Northern blot analyses showed abundant expression of calponin and SM1 without pioglitazone, but they were suppressed by pioglitazone to 11±4%, 15±5%, respectively. RT-PCR experiments revealed only SM1 mRNA was detected and easily downregulated with pioglitazone, while both SM1 and SM2 mRNA were detectable within the clones for at least 5 days without pioglitazone. CONCLUSIONS : The PPAR-γ agonist pioglitazone hampers the differentiation of BM-derived progenitor cells toward the smooth muscle lineage that may contribute to neointimal hyperplasia and may provide additional anti-atherosclerotic effects in the metabolic syndrome.
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