Endothelial nitric oxide synthase controls the expression of the angiogenesis inhibitor thrombospondin 2
Injury- and ischemia-induced angiogenesis is critical for tissue repair and requires nitric oxide (NO) derived from endothelial nitric oxide synthase (eNOS). We present evidence that NO induces angiogenesis by modulating the level of the angiogenesis inhibitor thrombospondin 2 (TSP2). TSP2 levels we...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2011-11, Vol.108 (46), p.E1137-E1145 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 108 |
| creator | MacLauchlan, Susan Yu, Jun Parrish, Marcus Asoulin, Tara A Schleicher, Michael Krady, Marie M Zeng, Jianmin Huang, Paul L Sessa, William C Kyriakides, Themis R |
| description | Injury- and ischemia-induced angiogenesis is critical for tissue repair and requires nitric oxide (NO) derived from endothelial nitric oxide synthase (eNOS). We present evidence that NO induces angiogenesis by modulating the level of the angiogenesis inhibitor thrombospondin 2 (TSP2). TSP2 levels were higher than WT in eNOS KO tissues in hind-limb ischemia and cutaneous wounds. In vitro studies confirmed that NO represses TSP2 promoter activity. Moreover, double-eNOS/TSP2 KO mice were generated and found to rescue the phenotype of eNOS KO mice. Studies in mice with knock-in constitutively active or inactive eNOS on the Akt-1 KO background showed that eNOS activity correlates with TSP2 levels. Our observations of NO-mediated regulation of angiogenesis via the suppression of TSP2 expression provide a description of improved eNOS KO phenotype by means other than restoring NO signaling. |
| doi_str_mv | 10.1073/pnas.1104357108 |
| format | Article |
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We present evidence that NO induces angiogenesis by modulating the level of the angiogenesis inhibitor thrombospondin 2 (TSP2). TSP2 levels were higher than WT in eNOS KO tissues in hind-limb ischemia and cutaneous wounds. In vitro studies confirmed that NO represses TSP2 promoter activity. Moreover, double-eNOS/TSP2 KO mice were generated and found to rescue the phenotype of eNOS KO mice. Studies in mice with knock-in constitutively active or inactive eNOS on the Akt-1 KO background showed that eNOS activity correlates with TSP2 levels. Our observations of NO-mediated regulation of angiogenesis via the suppression of TSP2 expression provide a description of improved eNOS KO phenotype by means other than restoring NO signaling.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1104357108</identifier><identifier>PMID: 21949402</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Angiogenesis ; Animals ; Biological Sciences ; Extracellular Matrix - metabolism ; Gene expression ; Gene Expression Regulation, Enzymologic ; HEK293 Cells ; Humans ; in vitro studies ; Ischemia ; Mice ; Mice, Knockout ; Neovascularization, Pathologic ; NIH 3T3 Cells ; Nitric oxide ; Nitric Oxide - metabolism ; nitric oxide synthase ; Nitric Oxide Synthase Type III - genetics ; Nitric Oxide Synthase Type III - metabolism ; phenotype ; PNAS Plus ; Proteins ; Rodents ; Signal Transduction ; Skin - pathology ; Thrombospondins - biosynthesis ; Thrombospondins - genetics ; tissue repair</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2011-11, Vol.108 (46), p.E1137-E1145</ispartof><rights>Copyright National Academy of Sciences Nov 15, 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c534t-10551622d11015ff5f384f1b6694bc925779a7548bed03891a106c1207b9e2e13</citedby><cites>FETCH-LOGICAL-c534t-10551622d11015ff5f384f1b6694bc925779a7548bed03891a106c1207b9e2e13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/108/46.cover.gif</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3219156/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3219156/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21949402$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>MacLauchlan, Susan</creatorcontrib><creatorcontrib>Yu, Jun</creatorcontrib><creatorcontrib>Parrish, Marcus</creatorcontrib><creatorcontrib>Asoulin, Tara A</creatorcontrib><creatorcontrib>Schleicher, Michael</creatorcontrib><creatorcontrib>Krady, Marie M</creatorcontrib><creatorcontrib>Zeng, Jianmin</creatorcontrib><creatorcontrib>Huang, Paul L</creatorcontrib><creatorcontrib>Sessa, William C</creatorcontrib><creatorcontrib>Kyriakides, Themis R</creatorcontrib><title>Endothelial nitric oxide synthase controls the expression of the angiogenesis inhibitor thrombospondin 2</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Injury- and ischemia-induced angiogenesis is critical for tissue repair and requires nitric oxide (NO) derived from endothelial nitric oxide synthase (eNOS). We present evidence that NO induces angiogenesis by modulating the level of the angiogenesis inhibitor thrombospondin 2 (TSP2). TSP2 levels were higher than WT in eNOS KO tissues in hind-limb ischemia and cutaneous wounds. In vitro studies confirmed that NO represses TSP2 promoter activity. Moreover, double-eNOS/TSP2 KO mice were generated and found to rescue the phenotype of eNOS KO mice. Studies in mice with knock-in constitutively active or inactive eNOS on the Akt-1 KO background showed that eNOS activity correlates with TSP2 levels. Our observations of NO-mediated regulation of angiogenesis via the suppression of TSP2 expression provide a description of improved eNOS KO phenotype by means other than restoring NO signaling.</description><subject>Angiogenesis</subject><subject>Animals</subject><subject>Biological Sciences</subject><subject>Extracellular Matrix - metabolism</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Enzymologic</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>in vitro studies</subject><subject>Ischemia</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Neovascularization, Pathologic</subject><subject>NIH 3T3 Cells</subject><subject>Nitric oxide</subject><subject>Nitric Oxide - metabolism</subject><subject>nitric oxide synthase</subject><subject>Nitric Oxide Synthase Type III - genetics</subject><subject>Nitric Oxide Synthase Type III - metabolism</subject><subject>phenotype</subject><subject>PNAS Plus</subject><subject>Proteins</subject><subject>Rodents</subject><subject>Signal Transduction</subject><subject>Skin - pathology</subject><subject>Thrombospondins - biosynthesis</subject><subject>Thrombospondins - genetics</subject><subject>tissue repair</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc1v1DAQxS0EotvCmRtYXHpKO-OPOL4goWr5kCpxgJ4tJ3E2rrL2Ymer9r_HYZcWOFny_ObpvXmEvEG4QFD8chdsvkAEwaVCaJ6RFYLGqhYanpMVAFNVI5g4Iac53wKAlg28JCcMtdAC2IqM69DHeXSTtxMNfk6-o_He947mhzCPNjvaxTCnOGVaMOrud8nl7GOgcfj9Y8PGx40LLvtMfRh96-eYyijFbRvzLobeB8pekReDnbJ7fXzPyM2n9Y-rL9X1t89frz5eV53kYq4QpMSasb6EQjkMcuCNGLCtay3aTjOplLZKiqZ1PfBGo0WoO2SgWu2YQ35GPhx0d_t26_rOFfN2MrvktzY9mGi9-XcS_Gg28c7wchSUdRE4Pwqk-HPv8my2PndummxwcZ-NBlnM1MgL-f4_8jbuUyjpFghl8bpAlweoSzHn5IZHKwhm6dAsHZqnDsvG278TPPJ_SisAPQLL5pNcY0Rt1ohcFeTdARlsNHaTfDY33xmgAMAGlFb8F-D1rQI</recordid><startdate>20111115</startdate><enddate>20111115</enddate><creator>MacLauchlan, Susan</creator><creator>Yu, Jun</creator><creator>Parrish, Marcus</creator><creator>Asoulin, Tara A</creator><creator>Schleicher, Michael</creator><creator>Krady, Marie M</creator><creator>Zeng, Jianmin</creator><creator>Huang, Paul L</creator><creator>Sessa, William C</creator><creator>Kyriakides, Themis R</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>FBQ</scope><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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20111115</creationdate><title>Endothelial nitric oxide synthase controls the expression of the angiogenesis inhibitor thrombospondin 2</title><author>MacLauchlan, Susan ; 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We present evidence that NO induces angiogenesis by modulating the level of the angiogenesis inhibitor thrombospondin 2 (TSP2). TSP2 levels were higher than WT in eNOS KO tissues in hind-limb ischemia and cutaneous wounds. In vitro studies confirmed that NO represses TSP2 promoter activity. Moreover, double-eNOS/TSP2 KO mice were generated and found to rescue the phenotype of eNOS KO mice. Studies in mice with knock-in constitutively active or inactive eNOS on the Akt-1 KO background showed that eNOS activity correlates with TSP2 levels. Our observations of NO-mediated regulation of angiogenesis via the suppression of TSP2 expression provide a description of improved eNOS KO phenotype by means other than restoring NO signaling.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>21949402</pmid><doi>10.1073/pnas.1104357108</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Angiogenesis Animals Biological Sciences Extracellular Matrix - metabolism Gene expression Gene Expression Regulation, Enzymologic HEK293 Cells Humans in vitro studies Ischemia Mice Mice, Knockout Neovascularization, Pathologic NIH 3T3 Cells Nitric oxide Nitric Oxide - metabolism nitric oxide synthase Nitric Oxide Synthase Type III - genetics Nitric Oxide Synthase Type III - metabolism phenotype PNAS Plus Proteins Rodents Signal Transduction Skin - pathology Thrombospondins - biosynthesis Thrombospondins - genetics tissue repair |
| title | Endothelial nitric oxide synthase controls the expression of the angiogenesis inhibitor thrombospondin 2 |
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