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Smooth muscle cells of human veins show an increased response to injury at valve sites.
https://asahikawa-med.repo.nii.ac.jp/records/5739
https://asahikawa-med.repo.nii.ac.jp/records/573989b02fc7-4dbc-40ee-be30-4ff5af791f7e
| 名前 / ファイル | ライセンス | アクション |
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6811.pdf (508.5 kB)
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| Item type | 学位論文 / Thesis or Dissertation_02(1) | |||||||||
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| 公開日 | 2017-10-05 | |||||||||
| タイトル | ||||||||||
| タイトル | Smooth muscle cells of human veins show an increased response to injury at valve sites. | |||||||||
| 言語 | en | |||||||||
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| 言語 | jpn | |||||||||
| 資源タイプ | ||||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_46ec | |||||||||
| 資源タイプ | thesis | |||||||||
| 著者 |
菊地, 信介
× 菊地, 信介
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| 著者 ローマ字 | ||||||||||
| Kikuchi, Shinsuke | ||||||||||
| 書誌情報 |
Journal of Vascular Surgery |
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| 収録物識別子タイプ | ISSN | |||||||||
| 収録物識別子 | 0741-5214 | |||||||||
| DOI | ||||||||||
| 識別子タイプ | DOI | |||||||||
| 関連識別子 | 10.1016/j.jvs.2017.03.447 | |||||||||
| 識別番号 その他 | ||||||||||
| 内容記述タイプ | Other | |||||||||
| 内容記述 | PMID：28647196 | |||||||||
| 学位授与番号 | ||||||||||
| 学位授与番号 | 10107A518 | |||||||||
| 学位授与年月日 | ||||||||||
| 学位授与年月日 | 2017-09-29 | |||||||||
| 学位名 | ||||||||||
| 学位名 | 博士（医学） | |||||||||
| 学位授与機関 | ||||||||||
| 学位授与機関名 | 旭川医科大学 | |||||||||
| 抄録 | ||||||||||
| 内容記述タイプ | Abstract | |||||||||
| 内容記述 | OBJECTIVE: \nVenous valves are essential but are prone to injury, thrombosis, and fibrosis. We compared the behavior and gene expression of smooth muscle cells (SMCs) in the valve sinus vs nonvalve sites to elucidate biologic differences associated with vein valves. METHODS: \nTissue explants of fresh human saphenous veins were prepared, and the migration of SMCs from explants of valve sinus vs nonvalve sinus areas was measured. Proliferation and death of SMCs were determined by staining for Ki67 and terminal deoxynucleotidyl transferase dUTP nick end labeling. Proliferation and migration of passaged valve vs nonvalve SMCs were determined by cell counts and using microchemotaxis chambers. Global gene expression in valve vs nonvalve intima-media was determined by RNA sequencing. RESULTS: \nValve SMCs demonstrated greater proliferation in tissue explants compared with nonvalve SMCs (19.3% ± 5.4% vs 6.8% ± 2.0% Ki67-positive nuclei at 4 days, respectively; mean ± standard error of the mean, five veins; P < .05). This was also true for migration (18.2 ± 2.7 vs 7.5 ± 3.0 migrated SMCs/explant at 6 days, respectively; 24 veins, 15 explants/vein; P < .0001). Cell death was not different (39.6% ± 16.1% vs 41.5% ± 16.0% terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells, respectively, at 4 days, five veins). Cultured valve SMCs also proliferated faster than nonvalve SMCs in response to platelet-derived growth factor subunit BB (2.9 ± 0.2-fold vs 2.1 ± 0.2-fold of control, respectively; P < .001; n = 5 pairs of cells). This was also true for migration (6.5 ± 1.2-fold vs 4.4 ± 0.8-fold of control, respectively; P < .001; n = 7 pairs of cells). Blockade of fibroblast growth factor 2 (FGF2) inhibited the increased responses of valve SMCs but had no effect on nonvalve SMCs. Exogenous FGF2 increased migration of valve but not of nonvalve SMCs. Unlike in the isolated, cultured cells, blockade of FGF2 in the tissue explants did not block migration of valve or nonvalve SMCs from the explants. Thirty-seven genes were differentially expressed by valve compared with nonvalve intimal-medial tissue (11 veins). Peptide-mediated inhibition of SEMA3A, one of the differentially expressed genes, increased the number of migrated SMCs of valve but not of nonvalve explants. CONCLUSIONS: \nValve compared with nonvalve SMCs have greater rates of migration and proliferation, which may in part explain the propensity for pathologic lesion formation in valves. Whereas FGF2 mediates these effects in cultured SMCs, the mediators of these stimulatory effects in the valve wall tissue remain unclear but may be among the differentially expressed genes discovered in this study. One of these genes, SEMA3A, mediates a valve-specific inhibitory effect on the injury response of valve SMCs. |
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| 内容記述タイプ | Other | |||||||||
| 内容記述 | application/pdf | |||||||||
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| 内容記述タイプ | Other | |||||||||
| 内容記述 | application/pdf | |||||||||
