Sirt7 Contributes to Myocardial Tissue Repair by Maintaining Transforming Growth Factor-β Signaling Pathway
BACKGROUND—Sirt7, 1 of the 7 members of the mammalian sirtuin family, promotes oncogenic transformation. Tumor growth and metastasis require fibrotic and angiogenic responses. Here, we investigated the role of Sirt7 in cardiovascular tissue repair process. METHODS AND RESULTS—In wild-type mice, Sirt...
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| Veröffentlicht in: | Circulation (New York, N.Y.) N.Y.), 2015-09, Vol.132 (12), p.1081-1093 |
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| creator | Araki, Satoshi Izumiya, Yasuhiro Rokutanda, Taku Ianni, Alessandro Hanatani, Shinsuke Kimura, Yuichi Onoue, Yoshiro Senokuchi, Takafumi Yoshizawa, Tatsuya Yasuda, Osamu Koitabashi, Norimichi Kurabayashi, Masahiko Braun, Thomas Bober, Eva Yamagata, Kazuya Ogawa, Hisao |
| description | BACKGROUND—Sirt7, 1 of the 7 members of the mammalian sirtuin family, promotes oncogenic transformation. Tumor growth and metastasis require fibrotic and angiogenic responses. Here, we investigated the role of Sirt7 in cardiovascular tissue repair process.
METHODS AND RESULTS—In wild-type mice, Sirt7 expression increased in response to acute cardiovascular injury, including myocardial infarction and hind-limb ischemia, particularly at the active wound healing site. Compared with wild-type mice, homozygous Sirt7-deficient (Sirt7) mice showed susceptibility to cardiac rupture after myocardial infarction, delayed blood flow recovery after hind-limb ischemia, and impaired wound healing after skin injury. Histological analysis showed reduced fibrosis, fibroblast differentiation, and inflammatory cell infiltration in the border zone of infarction in Sirt7 mice. In vitro, Sirt7 mouse–derived or Sirt7 siRNA–treated cardiac fibroblasts showed reduced transforming growth factor-β signal activation and low expression levels of fibrosis-related genes compared with wild-type mice–derived or control siRNA–treated cells. These changes were accompanied by reduction in transforming growth factor receptor I protein. Loss of Sirt7 activated autophagy in cardiac fibroblasts. Transforming growth factor-β receptor I downregulation induced by loss of Sirt7 was blocked by autophagy inhibitor, and interaction of Sirt7 with protein interacting with protein kinase-Cα was involved in this process.
CONCLUSION—Sirt7 maintains transforming growth factor receptor I by modulating autophagy and is involved in the tissue repair process. |
| doi_str_mv | 10.1161/CIRCULATIONAHA.114.014821 |
| format | Article |
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METHODS AND RESULTS—In wild-type mice, Sirt7 expression increased in response to acute cardiovascular injury, including myocardial infarction and hind-limb ischemia, particularly at the active wound healing site. Compared with wild-type mice, homozygous Sirt7-deficient (Sirt7) mice showed susceptibility to cardiac rupture after myocardial infarction, delayed blood flow recovery after hind-limb ischemia, and impaired wound healing after skin injury. Histological analysis showed reduced fibrosis, fibroblast differentiation, and inflammatory cell infiltration in the border zone of infarction in Sirt7 mice. In vitro, Sirt7 mouse–derived or Sirt7 siRNA–treated cardiac fibroblasts showed reduced transforming growth factor-β signal activation and low expression levels of fibrosis-related genes compared with wild-type mice–derived or control siRNA–treated cells. These changes were accompanied by reduction in transforming growth factor receptor I protein. Loss of Sirt7 activated autophagy in cardiac fibroblasts. Transforming growth factor-β receptor I downregulation induced by loss of Sirt7 was blocked by autophagy inhibitor, and interaction of Sirt7 with protein interacting with protein kinase-Cα was involved in this process.
CONCLUSION—Sirt7 maintains transforming growth factor receptor I by modulating autophagy and is involved in the tissue repair process.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/CIRCULATIONAHA.114.014821</identifier><identifier>PMID: 26202810</identifier><language>eng</language><publisher>United States: by the American College of Cardiology Foundation and the American Heart Association, Inc</publisher><subject>Animals ; Autophagy - drug effects ; Disease Models, Animal ; Fibroblasts - drug effects ; Fibroblasts - pathology ; Heart - physiology ; Hindlimb - blood supply ; In Vitro Techniques ; Ischemia - physiopathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myocardial Infarction - physiopathology ; Neovascularization, Physiologic - physiology ; Regeneration - physiology ; RNA, Small Interfering - pharmacology ; Signal Transduction - physiology ; Sirtuins - deficiency ; Sirtuins - genetics ; Sirtuins - physiology ; Transforming Growth Factor beta - physiology ; Wound Healing - physiology</subject><ispartof>Circulation (New York, N.Y.), 2015-09, Vol.132 (12), p.1081-1093</ispartof><rights>2015 by the American College of Cardiology Foundation and the American Heart Association, Inc.</rights><rights>2015 American Heart Association, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4694-6a00886db5ed4d333826a86c162576d880345f3359ce6585618226dc15b76aba3</citedby><cites>FETCH-LOGICAL-c4694-6a00886db5ed4d333826a86c162576d880345f3359ce6585618226dc15b76aba3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3687,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26202810$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Araki, Satoshi</creatorcontrib><creatorcontrib>Izumiya, Yasuhiro</creatorcontrib><creatorcontrib>Rokutanda, Taku</creatorcontrib><creatorcontrib>Ianni, Alessandro</creatorcontrib><creatorcontrib>Hanatani, Shinsuke</creatorcontrib><creatorcontrib>Kimura, Yuichi</creatorcontrib><creatorcontrib>Onoue, Yoshiro</creatorcontrib><creatorcontrib>Senokuchi, Takafumi</creatorcontrib><creatorcontrib>Yoshizawa, Tatsuya</creatorcontrib><creatorcontrib>Yasuda, Osamu</creatorcontrib><creatorcontrib>Koitabashi, Norimichi</creatorcontrib><creatorcontrib>Kurabayashi, Masahiko</creatorcontrib><creatorcontrib>Braun, Thomas</creatorcontrib><creatorcontrib>Bober, Eva</creatorcontrib><creatorcontrib>Yamagata, Kazuya</creatorcontrib><creatorcontrib>Ogawa, Hisao</creatorcontrib><title>Sirt7 Contributes to Myocardial Tissue Repair by Maintaining Transforming Growth Factor-β Signaling Pathway</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>BACKGROUND—Sirt7, 1 of the 7 members of the mammalian sirtuin family, promotes oncogenic transformation. Tumor growth and metastasis require fibrotic and angiogenic responses. Here, we investigated the role of Sirt7 in cardiovascular tissue repair process.
METHODS AND RESULTS—In wild-type mice, Sirt7 expression increased in response to acute cardiovascular injury, including myocardial infarction and hind-limb ischemia, particularly at the active wound healing site. Compared with wild-type mice, homozygous Sirt7-deficient (Sirt7) mice showed susceptibility to cardiac rupture after myocardial infarction, delayed blood flow recovery after hind-limb ischemia, and impaired wound healing after skin injury. Histological analysis showed reduced fibrosis, fibroblast differentiation, and inflammatory cell infiltration in the border zone of infarction in Sirt7 mice. In vitro, Sirt7 mouse–derived or Sirt7 siRNA–treated cardiac fibroblasts showed reduced transforming growth factor-β signal activation and low expression levels of fibrosis-related genes compared with wild-type mice–derived or control siRNA–treated cells. These changes were accompanied by reduction in transforming growth factor receptor I protein. Loss of Sirt7 activated autophagy in cardiac fibroblasts. Transforming growth factor-β receptor I downregulation induced by loss of Sirt7 was blocked by autophagy inhibitor, and interaction of Sirt7 with protein interacting with protein kinase-Cα was involved in this process.
CONCLUSION—Sirt7 maintains transforming growth factor receptor I by modulating autophagy and is involved in the tissue repair process.</description><subject>Animals</subject><subject>Autophagy - drug effects</subject><subject>Disease Models, Animal</subject><subject>Fibroblasts - drug effects</subject><subject>Fibroblasts - pathology</subject><subject>Heart - physiology</subject><subject>Hindlimb - blood supply</subject><subject>In Vitro Techniques</subject><subject>Ischemia - physiopathology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Myocardial Infarction - physiopathology</subject><subject>Neovascularization, Physiologic - physiology</subject><subject>Regeneration - physiology</subject><subject>RNA, Small Interfering - pharmacology</subject><subject>Signal Transduction - physiology</subject><subject>Sirtuins - deficiency</subject><subject>Sirtuins - genetics</subject><subject>Sirtuins - physiology</subject><subject>Transforming Growth Factor beta - physiology</subject><subject>Wound Healing - physiology</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUctu2zAQJIoWjZP2Fwr21osSvkUdDSEPA3ZdJM6ZWEl0zIQWHZKC4d_Kh_SbKsNpgR4Wi5md2QVmEfpOySWlil7Vs_v6cT5dzZY_p3fTkROXhArN6Ac0oZKJQkhefUQTQkhVlJyxM3Se0vMIFS_lZ3TGFCNMUzJB_sHFXOI69Dm6Zsg24Rzw4hBaiJ0Dj1cupcHie7sDF3FzwAtwfR7L9U94FaFP6xC3R3Abwz5v8A20OcTi9xt-cE89-OPoF-TNHg5f0Kc1-GS_vvcL9HhzvarvivnydlZP50UrVCUKBYRorbpG2k50nHPNFGjVUsVkqTqtCRdyzbmsWquklopqxlTXUtmUChrgF-jHae8uhtfBpmy2LrXWe-htGJKhJZUVlUKUo7Q6SdsYUop2bXbRbSEeDCXmGLb5P-yRE-YU9uj99n5maLa2--f8m-4oECfBPvhsY3rxw95Gs7Hg88aM7yCc0LJghEpSMUaKIyX4H5D4jGw</recordid><startdate>20150922</startdate><enddate>20150922</enddate><creator>Araki, Satoshi</creator><creator>Izumiya, Yasuhiro</creator><creator>Rokutanda, Taku</creator><creator>Ianni, Alessandro</creator><creator>Hanatani, Shinsuke</creator><creator>Kimura, Yuichi</creator><creator>Onoue, Yoshiro</creator><creator>Senokuchi, Takafumi</creator><creator>Yoshizawa, Tatsuya</creator><creator>Yasuda, Osamu</creator><creator>Koitabashi, Norimichi</creator><creator>Kurabayashi, Masahiko</creator><creator>Braun, Thomas</creator><creator>Bober, Eva</creator><creator>Yamagata, Kazuya</creator><creator>Ogawa, Hisao</creator><general>by the American College of Cardiology Foundation and the American Heart Association, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20150922</creationdate><title>Sirt7 Contributes to Myocardial Tissue Repair by Maintaining Transforming Growth Factor-β Signaling Pathway</title><author>Araki, Satoshi ; Izumiya, Yasuhiro ; Rokutanda, Taku ; Ianni, Alessandro ; Hanatani, Shinsuke ; Kimura, Yuichi ; Onoue, Yoshiro ; Senokuchi, Takafumi ; Yoshizawa, Tatsuya ; Yasuda, Osamu ; Koitabashi, Norimichi ; Kurabayashi, Masahiko ; Braun, Thomas ; Bober, Eva ; Yamagata, Kazuya ; Ogawa, Hisao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4694-6a00886db5ed4d333826a86c162576d880345f3359ce6585618226dc15b76aba3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Autophagy - drug effects</topic><topic>Disease Models, Animal</topic><topic>Fibroblasts - drug effects</topic><topic>Fibroblasts - pathology</topic><topic>Heart - physiology</topic><topic>Hindlimb - blood supply</topic><topic>In Vitro Techniques</topic><topic>Ischemia - physiopathology</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Myocardial Infarction - physiopathology</topic><topic>Neovascularization, Physiologic - physiology</topic><topic>Regeneration - physiology</topic><topic>RNA, Small Interfering - pharmacology</topic><topic>Signal Transduction - physiology</topic><topic>Sirtuins - deficiency</topic><topic>Sirtuins - genetics</topic><topic>Sirtuins - physiology</topic><topic>Transforming Growth Factor beta - physiology</topic><topic>Wound Healing - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Araki, Satoshi</creatorcontrib><creatorcontrib>Izumiya, Yasuhiro</creatorcontrib><creatorcontrib>Rokutanda, Taku</creatorcontrib><creatorcontrib>Ianni, Alessandro</creatorcontrib><creatorcontrib>Hanatani, Shinsuke</creatorcontrib><creatorcontrib>Kimura, Yuichi</creatorcontrib><creatorcontrib>Onoue, Yoshiro</creatorcontrib><creatorcontrib>Senokuchi, Takafumi</creatorcontrib><creatorcontrib>Yoshizawa, Tatsuya</creatorcontrib><creatorcontrib>Yasuda, Osamu</creatorcontrib><creatorcontrib>Koitabashi, Norimichi</creatorcontrib><creatorcontrib>Kurabayashi, Masahiko</creatorcontrib><creatorcontrib>Braun, Thomas</creatorcontrib><creatorcontrib>Bober, Eva</creatorcontrib><creatorcontrib>Yamagata, Kazuya</creatorcontrib><creatorcontrib>Ogawa, Hisao</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Circulation (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Araki, Satoshi</au><au>Izumiya, Yasuhiro</au><au>Rokutanda, Taku</au><au>Ianni, Alessandro</au><au>Hanatani, Shinsuke</au><au>Kimura, Yuichi</au><au>Onoue, Yoshiro</au><au>Senokuchi, Takafumi</au><au>Yoshizawa, Tatsuya</au><au>Yasuda, Osamu</au><au>Koitabashi, Norimichi</au><au>Kurabayashi, Masahiko</au><au>Braun, Thomas</au><au>Bober, Eva</au><au>Yamagata, Kazuya</au><au>Ogawa, Hisao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sirt7 Contributes to Myocardial Tissue Repair by Maintaining Transforming Growth Factor-β Signaling Pathway</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>2015-09-22</date><risdate>2015</risdate><volume>132</volume><issue>12</issue><spage>1081</spage><epage>1093</epage><pages>1081-1093</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><abstract>BACKGROUND—Sirt7, 1 of the 7 members of the mammalian sirtuin family, promotes oncogenic transformation. Tumor growth and metastasis require fibrotic and angiogenic responses. Here, we investigated the role of Sirt7 in cardiovascular tissue repair process.
METHODS AND RESULTS—In wild-type mice, Sirt7 expression increased in response to acute cardiovascular injury, including myocardial infarction and hind-limb ischemia, particularly at the active wound healing site. Compared with wild-type mice, homozygous Sirt7-deficient (Sirt7) mice showed susceptibility to cardiac rupture after myocardial infarction, delayed blood flow recovery after hind-limb ischemia, and impaired wound healing after skin injury. Histological analysis showed reduced fibrosis, fibroblast differentiation, and inflammatory cell infiltration in the border zone of infarction in Sirt7 mice. In vitro, Sirt7 mouse–derived or Sirt7 siRNA–treated cardiac fibroblasts showed reduced transforming growth factor-β signal activation and low expression levels of fibrosis-related genes compared with wild-type mice–derived or control siRNA–treated cells. These changes were accompanied by reduction in transforming growth factor receptor I protein. Loss of Sirt7 activated autophagy in cardiac fibroblasts. Transforming growth factor-β receptor I downregulation induced by loss of Sirt7 was blocked by autophagy inhibitor, and interaction of Sirt7 with protein interacting with protein kinase-Cα was involved in this process.
CONCLUSION—Sirt7 maintains transforming growth factor receptor I by modulating autophagy and is involved in the tissue repair process.</abstract><cop>United States</cop><pub>by the American College of Cardiology Foundation and the American Heart Association, Inc</pub><pmid>26202810</pmid><doi>10.1161/CIRCULATIONAHA.114.014821</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; American Heart Association Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Complete |
| subjects | Animals Autophagy - drug effects Disease Models, Animal Fibroblasts - drug effects Fibroblasts - pathology Heart - physiology Hindlimb - blood supply In Vitro Techniques Ischemia - physiopathology Male Mice Mice, Inbred C57BL Mice, Knockout Myocardial Infarction - physiopathology Neovascularization, Physiologic - physiology Regeneration - physiology RNA, Small Interfering - pharmacology Signal Transduction - physiology Sirtuins - deficiency Sirtuins - genetics Sirtuins - physiology Transforming Growth Factor beta - physiology Wound Healing - physiology |
| title | Sirt7 Contributes to Myocardial Tissue Repair by Maintaining Transforming Growth Factor-β Signaling Pathway |
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