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Homozygotes of ADM knockout mice (ADM-/-) were lethal at mid-gestation with abnormalities of vascular development and this finding clarified the angiogenic potency of ADM. Calcitonin gene-related peptide (CGRP), which has a structure and function similar to that of ADM, has been identified as a family peptide of ADM. Unlike ADM-/-, CGRP-/- were apparently normal. Therefore, the study of knockout mice first clarified the distinctly different physiological roles between ADM and CGRP. In contrast, heterozygotes of ADM knockout mice (ADM+/-) were alive but showed blood pressure elevation, reduced neovascularization, and enhanced neointimal formation by arterial injury. Based on these observations, there was hope ADM would have a therapeutic use. However, ADM has a short half-life in the blood stream and its application in chronic disease has limitations. Therefore, we focused on the ADM receptor system. The calcitonin-receptor-like receptor (CLR), which is the ADM receptor, associates with one of the accessory proteins, called receptor activity-modifying proteins (RAMPs). By interacting with RAMP1, CLR exhibits a high affinity for CGRP, whereas by interacting with either RAMP2 or -3, CLR exhibits a high affinity for ADM. We generated RAMP knockout mice and found that vascular phenotypes similar to ADM-/- were reproduced only in RAMP2-/-. This shows that RAMP2 is the key determinant of the vascular functions of ADM. RAMP2 could be an attractive therapeutic target in cardiovascular diseases.", "subitem_description_type": "Abstract"}]}, "item_6_description_30": {"attribute_name": "資源タイプ（コンテンツの種類）", "attribute_value_mlt": [{"subitem_description": "Article", "subitem_description_type": "Other"}]}, "item_6_description_5": {"attribute_name": "引用", "attribute_value_mlt": [{"subitem_description": "CURRENT PROTEIN \u0026 PEPTIDE SCIENCE. 14(5):347-357 (2013)", "subitem_description_type": "Other"}]}, "item_6_link_3": {"attribute_name": "信州大学研究者総覧へのリンク", "attribute_value_mlt": [{"subitem_link_text": "Shindo, Takayuki", "subitem_link_url": "http://soar-rd.shinshu-u.ac.jp/profile/ja.OCLpOayV.html"}, {"subitem_link_text": "Sakurai, Takayuki", "subitem_link_url": "http://soar-rd.shinshu-u.ac.jp/profile/ja.jaLUuNkh.html"}, {"subitem_link_text": "Kamiyoshi, Akiko", "subitem_link_url": "http://soar-rd.shinshu-u.ac.jp/profile/ja.OpLVuNkh.html"}]}, "item_6_link_67": {"attribute_name": "WoS", "attribute_value_mlt": [{"subitem_link_text": "Web of Science", "subitem_link_url": "http://gateway.isiknowledge.com/gateway/Gateway.cgi?\u0026GWVersion=2\u0026SrcAuth=ShinshuUniv\u0026SrcApp=ShinshuUniv\u0026DestLinkType=FullRecord\u0026DestApp=WOS\u0026KeyUT=000324167600001"}]}, "item_6_publisher_4": {"attribute_name": "出版者", "attribute_value_mlt": [{"subitem_publisher": "BENTHAM SCIENCE PUBL LTD"}]}, "item_6_relation_47": {"attribute_name": "PubMed", "attribute_value_mlt": [{"subitem_relation_name": [{"subitem_relation_name_text": "23745699"}], "subitem_relation_type_id": {"subitem_relation_type_id_text": "https://pubmed.ncbi.nlm.nih.gov/23745699", "subitem_relation_type_select": "PMID"}}]}, "item_6_relation_48": {"attribute_name": "DOI", "attribute_value_mlt": [{"subitem_relation_name": [{"subitem_relation_name_text": "10.2174/13892037113149990052"}], "subitem_relation_type_id": {"subitem_relation_type_id_text": "https://doi.org/10.2174/13892037113149990052", "subitem_relation_type_select": "DOI"}}]}, "item_6_rights_62": {"attribute_name": "権利", "attribute_value_mlt": [{"subitem_rights": "© 2013 Bentham Science Publishers"}]}, "item_6_select_64": {"attribute_name": "著者版フラグ", "attribute_value_mlt": [{"subitem_select_item": "author"}]}, "item_6_source_id_35": {"attribute_name": "ISSN", "attribute_value_mlt": [{"subitem_source_identifier": "1389-2037", "subitem_source_identifier_type": "PISSN"}]}, "item_6_source_id_39": {"attribute_name": "NII ISSN", "attribute_value_mlt": [{"subitem_source_identifier": "1389-2037", "subitem_source_identifier_type": "PISSN"}]}, "item_6_source_id_40": {"attribute_name": "書誌レコードID", "attribute_value_mlt": [{"subitem_source_identifier": "AA11692455", "subitem_source_identifier_type": "NCID"}]}, "item_6_text_69": {"attribute_name": "wosonly authkey", "attribute_value_mlt": [{"subitem_text_value": "Adrenomedullin; receptor activity-modifying proteins; knockout mouse; angiogenesis; lymphangiogenesis; endothelial cell"}]}, "item_6_text_70": {"attribute_name": "wosonly keywords", "attribute_value_mlt": [{"subitem_text_value": "GENE-RELATED PEPTIDE; ACTIVITY-MODIFYING PROTEINS; SMOOTH-MUSCLE-CELLS; ENDOTHELIAL-CELLS; CALCITONIN-GENE; ENDOGENOUS ADRENOMEDULLIN; COLLATERAL DEVELOPMENT; HYPOTENSIVE PEPTIDE; ACUTE-ISCHEMIA; HEART-FAILURE"}]}, "item_6_textarea_68": {"attribute_name": "wosonly abstract", "attribute_value_mlt": [{"subitem_textarea_value": "Adrenomedullin (ADM), originally identified as a vasodilating peptide, is now recognized to be a pleiotropic molecule involved in both the pathogenesis of cardiovascular diseases and circulatory homeostasis. Homozygotes of ADM knockout mice (ADM-/-) were lethal at mid-gestation with abnormalities of vascular development and this finding clarified the angiogenic potency of ADM. Calcitonin gene-related peptide (CGRP), which has a structure and function similar to that of ADM, has been identified as a family peptide of ADM. Unlike ADM-/-, CGRP-/- were apparently normal. Therefore, the study of knockout mice first clarified the distinctly different physiological roles between ADM and CGRP. In contrast, heterozygotes of ADM knockout mice (ADM+/-) were alive but showed blood pressure elevation, reduced neovascularization, and enhanced neointimal formation by arterial injury. Based on these observations, there was hope ADM would have a therapeutic use. However, ADM has a short half-life in the blood stream and its application in chronic disease has limitations. Therefore, we focused on the ADM receptor system. The calcitonin-receptor-like receptor (CLR), which is the ADM receptor, associates with one of the accessory proteins, called receptor activity-modifying proteins (RAMPs). By interacting with RAMP1, CLR exhibits a high affinity for CGRP, whereas by interacting with either RAMP2 or -3, CLR exhibits a high affinity for ADM. We generated RAMP knockout mice and found that vascular phenotypes similar to ADM-/- were reproduced only in RAMP2-/-. This shows that RAMP2 is the key determinant of the vascular functions of ADM. RAMP2 could be an attractive therapeutic target in cardiovascular diseases."}]}, "item_creator": {"attribute_name": "著者", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "Shindo, Takayuki", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "104611", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Sakurai, Takayuki", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "104612", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Kamiyoshi, Akiko", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "104613", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Ichikawa-Shindo, Yuka", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "104614", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Shimoyama, Natsumi", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "104615", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Iinuma, Nobuyoshi", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "104616", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Arai, Takuma", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "104617", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Miyagawa, Shinichi", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "104618", "nameIdentifierScheme": "WEKO"}]}]}, "item_files": {"attribute_name": "ファイル情報", "attribute_type": "file", "attribute_value_mlt": [{"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2017-12-28"}], "displaytype": "detail", "download_preview_message": "", "file_order": 0, "filename": "Regulation_ Adrenomedullin_its_Family_Peptide_RAMP_System.pdf", "filesize": [{"value": "1.7 MB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensefree": "© 2013 Bentham Science Publishers", "licensetype": "license_note", "mimetype": "application/pdf", "size": 1700000.0, "url": {"label": "Regulation_ Adrenomedullin_its_Family_Peptide_RAMP_System.pdf", "url": "https://soar-ir.repo.nii.ac.jp/record/19351/files/Regulation_ Adrenomedullin_its_Family_Peptide_RAMP_System.pdf"}, "version_id": "15eb7fbe-a35f-4ae3-9547-0ebe445bc36a"}]}, "item_keyword": {"attribute_name": "キーワード", "attribute_value_mlt": [{"subitem_subject": "Adrenomedullin", "subitem_subject_scheme": "Other"}, {"subitem_subject": "receptor activity-modifying proteins", "subitem_subject_scheme": "Other"}, {"subitem_subject": "knockout mouse", "subitem_subject_scheme": "Other"}, {"subitem_subject": "angiogenesis", "subitem_subject_scheme": "Other"}, {"subitem_subject": "lymphangiogenesis", "subitem_subject_scheme": "Other"}, {"subitem_subject": "endothelial cell", "subitem_subject_scheme": "Other"}]}, "item_language": {"attribute_name": "言語", "attribute_value_mlt": [{"subitem_language": "jpn"}]}, "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": "Regulation of Adrenomedullin and its Family Peptide by RAMP System - Lessons from Genetically Engineered Mice", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "Regulation of Adrenomedullin and its Family Peptide by RAMP System - Lessons from Genetically Engineered Mice", "subitem_title_language": "ja"}]}, "item_type_id": "6", "owner": "1", "path": ["462"], "permalink_uri": "http://hdl.handle.net/10091/00020112", "pubdate": {"attribute_name": "PubDate", "attribute_value": "2017-12-28"}, "publish_date": "2017-12-28", "publish_status": "0", "recid": "19351", "relation": {}, "relation_version_is_last": true, "title": ["Regulation of Adrenomedullin and its Family Peptide by RAMP System - Lessons from Genetically Engineered Mice"], "weko_shared_id": -1}