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However, the effects of hydrophilic statin (pravastatin) on EPC kinetics remain to be investigated. Here, we investigated whether pravastatin stimulates EPC kinetics via intracellular signal transduction following its uptake by EPCs. Pravastatin uptake by cultured EPCs was measured by 14C-radio labeled molecules, and was compared with that by HepG2 cells as a negative control (^*29.15 ± 2.80 vs 7.82 ± 0.47 count/min/mg protein, ^*p\u003c0.0001). EPC migratory activity toward pravastatin was significantly stimulated when compared with the vehicle group. EPC antiapoptotic assay by DAPI staining and cell death detection ELISA demonstrated abrogated apoptosis in the pravastatin group. In addition, pravastatin activated the PI-3-kinase/Akt pathway leading to endothelial nitricoxide synthase eNOS) activation. Co-treatment with PI-3/Akt inhibitors blocked pravastatin-induced Akt activation, indicating Akt activation through PI-3-kinase phosphorylation. When pravastatin was orally administered to nude mice, the number of circulating EPCs increased in a time-dependent fashion. These findings suggest that hydrophilic pravastatin exerts provasculogenic effects via the upregualtion of EPC migration and survival through PI-3-kinase/Akt/eNOS pathway activation following intracellular uptake.", "subitem_description_type": "Abstract"}]}, "item_10001_full_name_3": {"attribute_name": "著者別名", "attribute_value_mlt": [{"nameIdentifiers": [{"nameIdentifier": "296339", "nameIdentifierScheme": "WEKO"}], "names": [{"name": "石見, 陽"}]}, {"nameIdentifiers": [{"nameIdentifier": "296340", "nameIdentifierScheme": "WEKO"}], "names": [{"name": "増田, 治史"}]}, {"nameIdentifiers": [{"nameIdentifier": "296341", "nameIdentifierScheme": "WEKO"}], "names": [{"name": "鶴見, 由起夫"}]}, {"nameIdentifiers": [{"nameIdentifier": "296342", "nameIdentifierScheme": "WEKO"}], "names": [{"name": "笠貫, 宏"}]}, {"nameIdentifiers": [{"nameIdentifier": "296343", "nameIdentifierScheme": "WEKO"}], "names": [{"name": "浅原, 孝之"}]}]}, "item_10001_publisher_8": {"attribute_name": "出版者", "attribute_value_mlt": [{"subitem_publisher": "東京女子医科大学学会"}]}, "item_10001_source_id_11": {"attribute_name": "NCID", "attribute_value_mlt": [{"subitem_source_identifier": "AN00161368", "subitem_source_identifier_type": "NCID"}]}, "item_10001_source_id_9": {"attribute_name": "ISSN", "attribute_value_mlt": [{"subitem_source_identifier": "0040-9022", "subitem_source_identifier_type": "ISSN"}]}, "item_10001_subject_47": {"attribute_name": "著者キーワード", "attribute_value_mlt": [{"subitem_subject": "EPC", "subitem_subject_scheme": "Other"}, {"subitem_subject": "pravastatin", "subitem_subject_scheme": "Other"}, {"subitem_subject": "vasculogenesis", "subitem_subject_scheme": "Other"}, {"subitem_subject": "angiogenesis", "subitem_subject_scheme": "Other"}, {"subitem_subject": "eNOS", "subitem_subject_scheme": "Other"}]}, "item_10001_text_35": {"attribute_name": "著者所属", "attribute_value_mlt": [{"subitem_text_value": "Department of Regenerative Medicine Science, Tokai University School of Medicine:Department of Cardiology, Tokyo Women\u0027s Medical University, School of Medicine"}, {"subitem_text_value": "Department of Regenerative Medicine Science, Tokai University School of Medicine"}, {"subitem_text_value": "Department of Cardiology, Tokyo Women\u0027s Medical University, School of Medicine"}, {"subitem_text_value": "Department of Cardiology, Tokyo Women\u0027s Medical University, School of Medicine"}, {"subitem_text_value": "Department of Regenerative Medicine Science, Tokai University School of Medicine:Stem Cell Translational Research, Kobe Institute of Biomedical Research and Innovation, RIKEN Center of Developmental Biology"}, {"subitem_text_value": "東海大学医学部再生医療科学:東京女子医科大学医学部循環器内科学"}, {"subitem_text_value": "東海大学医学部再生医療科学"}, {"subitem_text_value": "東京女子医科大学医学部循環器内科学"}, {"subitem_text_value": "東京女子医科大学医学部循環器内科学"}, {"subitem_text_value": "東海大学医学部再生医療科学:理化学研究所神戸研究所幹細胞医療応用研究チーム"}]}, "item_10001_version_type_20": {"attribute_name": "著者版フラグ", "attribute_value_mlt": [{"subitem_version_resource": "http://purl.org/coar/version/c_970fb48d4fbd8a85", "subitem_version_type": "VoR"}]}, "item_files": {"attribute_name": "ファイル情報", "attribute_type": "file", "attribute_value_mlt": [{"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2017-08-22"}], "displaytype": "detail", "download_preview_message": "", "file_order": 0, "filename": "KJ00006024387.pdf", "filesize": [{"value": "871.3 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_free", "mimetype": "application/pdf", "size": 871300.0, "url": {"label": "KJ00006024387.pdf", "url": "https://twinkle.repo.nii.ac.jp/record/20193/files/KJ00006024387.pdf"}, "version_id": "e70354b4-d7dd-4cbc-bf94-b87d008227df"}]}, "item_language": {"attribute_name": "言語", "attribute_value_mlt": [{"subitem_language": "eng"}]}, "item_resource_type": {"attribute_name": "資源タイプ", "attribute_value_mlt": [{"resourcetype": "journal article", "resourceuri": "http://purl.org/coar/resource_type/c_6501"}]}, "item_title": "Effects of Hydrophilic Statin, Pravastatin, on Vasculogenic Properties of Endothelial Progenitor Cells", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "Effects of Hydrophilic Statin, Pravastatin, on Vasculogenic Properties of Endothelial Progenitor Cells"}]}, "item_type_id": "10001", "owner": "3", "path": ["2023"], "permalink_uri": "http://hdl.handle.net/10470/27492", "pubdate": {"attribute_name": "公開日", "attribute_value": "2010-08-10"}, "publish_date": "2010-08-10", "publish_status": "0", "recid": "20193", "relation": {}, "relation_version_is_last": true, "title": ["Effects of Hydrophilic Statin, Pravastatin, on Vasculogenic Properties of Endothelial Progenitor Cells"], "weko_shared_id": -1}
Effects of Hydrophilic Statin, Pravastatin, on Vasculogenic Properties of Endothelial Progenitor Cells
http://hdl.handle.net/10470/27492
http://hdl.handle.net/10470/27492f6a70ea4-daf2-4553-b8e0-4ca62b301e1b
名前 / ファイル | ライセンス | アクション |
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KJ00006024387.pdf (871.3 kB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2010-08-10 | |||||
タイトル | ||||||
タイトル | Effects of Hydrophilic Statin, Pravastatin, on Vasculogenic Properties of Endothelial Progenitor Cells | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
別タイトル | ||||||
その他のタイトル | 血管内皮前駆細胞の血管新生作用に対する水溶性スタチン(プラバスタチン)の影響 | |||||
著者名 |
IWAMI, Yo
× IWAMI, Yo× MASUDA, Haruchika× TSURUMI, Yukio× KASANUKI, Hiroshi× ASAHARA, Takayuki |
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著者別名 | ||||||
姓名 | 石見, 陽 | |||||
著者別名 | ||||||
姓名 | 増田, 治史 | |||||
著者別名 | ||||||
姓名 | 鶴見, 由起夫 | |||||
著者別名 | ||||||
姓名 | 笠貫, 宏 | |||||
著者別名 | ||||||
姓名 | 浅原, 孝之 | |||||
出版者 | ||||||
出版者 | 東京女子医科大学学会 | |||||
受付日付 | ||||||
日付 | 2010-08-10 | |||||
日付タイプ | Created | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 0040-9022 | |||||
NCID | ||||||
収録物識別子タイプ | NCID | |||||
収録物識別子 | AN00161368 | |||||
書誌情報 |
東京女子医科大学雑誌 巻 77, 号 6, p. 306-314, 発行日 2007-06 |
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著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | 脂溶性HMG-CoAリダクターゼ・インヒビター(脂溶性スタチン)による血管内皮前駆細胞(EPC)動員,治療的血管形成作用改善効果は多数の報告がされている.しかしながら水溶性スタチン(プラバスタチン)のEPCに対する作用は充分に解明されていない.本研究により,水溶性スタチンがEPC内に取り込まれ,細胞内シグナルを刺激することでEPC動態に作用することを明らかとする.^<14>C標識プラバスタチンにより,HepG2細胞を対照群としてEPC内へのプラバスタチン取り込みを測定した結果,EPC群は有意にプラバスタチンを細胞内に取り込んだ(*29.15±2.80vs7.82±0.47count/min/mg protein,^*p<0.000).EPCの遊走能測定実験において,プラバスタチン群は対照群と比較して,有意に遊走能を増加させた.また,抗アポトーシス作用測定実験において,プラバスタチン群は対照群と比較して有意にアポトーシスを抑制していた.更に,ウェスタンブロットを行ったところ,EPC内においてプラバスタチンはPI-3-kinase/Akt経路を刺激することにより,eNOSのリン酸化を行うことが判明した.この反応はPI-3/Akt阻害剤により消失することにより,PI-3-kinase/Akt経路依存性であることが確かめられた.In vivoにおいて,プラバスタチンをマウスに投与したところ,プラバスタチンは対照群と比較して投与時間依存性に末梢血液中のEPC数を増加させることが判明した.これらの結果により,水溶性スタチンであるプラバスタチンは,EPC内のPI-3-kinase/Akt/eNOS経路により,EPC遊走能・抗アポトーシス作用を活性化することが明らかとなった. | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Previous studies have demonstrated that hydrophobic hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) mobilize circulating endothelial progenitor cells (EPCs), and contribute to therapeutic vasculogenesis. However, the effects of hydrophilic statin (pravastatin) on EPC kinetics remain to be investigated. Here, we investigated whether pravastatin stimulates EPC kinetics via intracellular signal transduction following its uptake by EPCs. Pravastatin uptake by cultured EPCs was measured by 14C-radio labeled molecules, and was compared with that by HepG2 cells as a negative control (^*29.15 ± 2.80 vs 7.82 ± 0.47 count/min/mg protein, ^*p<0.0001). EPC migratory activity toward pravastatin was significantly stimulated when compared with the vehicle group. EPC antiapoptotic assay by DAPI staining and cell death detection ELISA demonstrated abrogated apoptosis in the pravastatin group. In addition, pravastatin activated the PI-3-kinase/Akt pathway leading to endothelial nitricoxide synthase eNOS) activation. Co-treatment with PI-3/Akt inhibitors blocked pravastatin-induced Akt activation, indicating Akt activation through PI-3-kinase phosphorylation. When pravastatin was orally administered to nude mice, the number of circulating EPCs increased in a time-dependent fashion. These findings suggest that hydrophilic pravastatin exerts provasculogenic effects via the upregualtion of EPC migration and survival through PI-3-kinase/Akt/eNOS pathway activation following intracellular uptake. | |||||
著者所属 | ||||||
Department of Regenerative Medicine Science, Tokai University School of Medicine:Department of Cardiology, Tokyo Women's Medical University, School of Medicine | ||||||
著者所属 | ||||||
Department of Regenerative Medicine Science, Tokai University School of Medicine | ||||||
著者所属 | ||||||
Department of Cardiology, Tokyo Women's Medical University, School of Medicine | ||||||
著者所属 | ||||||
Department of Cardiology, Tokyo Women's Medical University, School of Medicine | ||||||
著者所属 | ||||||
Department of Regenerative Medicine Science, Tokai University School of Medicine:Stem Cell Translational Research, Kobe Institute of Biomedical Research and Innovation, RIKEN Center of Developmental Biology | ||||||
著者所属 | ||||||
東海大学医学部再生医療科学:東京女子医科大学医学部循環器内科学 | ||||||
著者所属 | ||||||
東海大学医学部再生医療科学 | ||||||
著者所属 | ||||||
東京女子医科大学医学部循環器内科学 | ||||||
著者所属 | ||||||
東京女子医科大学医学部循環器内科学 | ||||||
著者所属 | ||||||
東海大学医学部再生医療科学:理化学研究所神戸研究所幹細胞医療応用研究チーム | ||||||
著者キーワード | ||||||
主題Scheme | Other | |||||
主題 | EPC | |||||
著者キーワード | ||||||
主題Scheme | Other | |||||
主題 | pravastatin | |||||
著者キーワード | ||||||
主題Scheme | Other | |||||
主題 | vasculogenesis | |||||
著者キーワード | ||||||
主題Scheme | Other | |||||
主題 | angiogenesis | |||||
著者キーワード | ||||||
主題Scheme | Other | |||||
主題 | eNOS |