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Proangiogenesis Action of the Thyroid Hormone Analog 3,5-Diiodothyropropionic Acid (DITPA) Is Initiated at the Cell Surface and Is Integrin Mediated
We have recently described the proangiogenesis effects of thyroid hormone in the chick chorioallantoic membrane (CAM) model. Generation of new blood vessels from existing vessels was promoted 2- to 3-fold by either T4 or T3 at 10−8–10−7 m total hormone concentrations. In the present studies, nanomol...
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Published in: | Endocrinology (Philadelphia) 2006-04, Vol.147 (4), p.1602-1607 |
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description | We have recently described the proangiogenesis effects of thyroid hormone in the chick chorioallantoic membrane (CAM) model. Generation of new blood vessels from existing vessels was promoted 2- to 3-fold by either T4 or T3 at 10−8–10−7 m total hormone concentrations. In the present studies, nanomolar concentrations of 3,5-diiodothyropropionic acid (DITPA), a thyroid hormone analog with inotropic but not chronotropic properties, exhibited potent proangiogenic activity that was comparable to that obtained with T3 and T4 in both the CAM model and in an in vitro three-dimensional human microvascular endothelial sprouting assay. The proangiogenesis effect of DITPA was inhibited by tetraiodothyroacetic acid, a thyroid hormone analog that competes with T4 and T3 for a novel cell surface hormone receptor site on integrin αvβ3. The thyroid hormone analogs DITPA, T4, and T4-agarose, as well as basic fibroblast growth factor (b-FGF) and vascular endothelial cell growth factor, demonstrated comparable proangiogenic effects in the CAM model and in the three-dimensional human microvascular endothelial sprouting model. The proangiogenesis effect of either DITPA or b-FGF was blocked by PD 98059, an inhibitor of the ERK1/2 signal transduction cascade. Additionally, a specific integrin αvβ3 small molecule antagonist, XT199, effectively inhibited the proangiogenesis effect of DITPA and b-FGF. Thus, the proangiogenesis actions of thyroid hormone and its analog DITPA are initiated at the plasma membrane, apparently at integrin αvβ3, and are MAPK dependent. |
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Psychology ; Humans ; Integrin alphaVbeta3 - physiology ; MAP Kinase Signaling System - physiology ; Mitogen-Activated Protein Kinase 1 - physiology ; Mitogen-Activated Protein Kinase 3 - physiology ; Neovascularization, Physiologic - drug effects ; Propionates - pharmacology ; Thyroxine - analogs & derivatives ; Thyroxine - pharmacology ; Vertebrates: endocrinology</subject><ispartof>Endocrinology (Philadelphia), 2006-04, Vol.147 (4), p.1602-1607</ispartof><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c401t-90e1e3ab3cae2799956db73f4e11778aad6e8cc8d27c779ab79130c75f7a11ee3</citedby><cites>FETCH-LOGICAL-c401t-90e1e3ab3cae2799956db73f4e11778aad6e8cc8d27c779ab79130c75f7a11ee3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17645203$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16384862$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mousa, Shaker A</creatorcontrib><creatorcontrib>O’Connor, Laura</creatorcontrib><creatorcontrib>Davis, Faith B</creatorcontrib><creatorcontrib>Davis, Paul J</creatorcontrib><title>Proangiogenesis Action of the Thyroid Hormone Analog 3,5-Diiodothyropropionic Acid (DITPA) Is Initiated at the Cell Surface and Is Integrin Mediated</title><title>Endocrinology (Philadelphia)</title><addtitle>Endocrinology</addtitle><description>We have recently described the proangiogenesis effects of thyroid hormone in the chick chorioallantoic membrane (CAM) model. Generation of new blood vessels from existing vessels was promoted 2- to 3-fold by either T4 or T3 at 10−8–10−7 m total hormone concentrations. In the present studies, nanomolar concentrations of 3,5-diiodothyropropionic acid (DITPA), a thyroid hormone analog with inotropic but not chronotropic properties, exhibited potent proangiogenic activity that was comparable to that obtained with T3 and T4 in both the CAM model and in an in vitro three-dimensional human microvascular endothelial sprouting assay. The proangiogenesis effect of DITPA was inhibited by tetraiodothyroacetic acid, a thyroid hormone analog that competes with T4 and T3 for a novel cell surface hormone receptor site on integrin αvβ3. The thyroid hormone analogs DITPA, T4, and T4-agarose, as well as basic fibroblast growth factor (b-FGF) and vascular endothelial cell growth factor, demonstrated comparable proangiogenic effects in the CAM model and in the three-dimensional human microvascular endothelial sprouting model. The proangiogenesis effect of either DITPA or b-FGF was blocked by PD 98059, an inhibitor of the ERK1/2 signal transduction cascade. Additionally, a specific integrin αvβ3 small molecule antagonist, XT199, effectively inhibited the proangiogenesis effect of DITPA and b-FGF. Thus, the proangiogenesis actions of thyroid hormone and its analog DITPA are initiated at the plasma membrane, apparently at integrin αvβ3, and are MAPK dependent.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cell Membrane - drug effects</subject><subject>Chick Embryo</subject><subject>Diiodothyronines - pharmacology</subject><subject>Fibroblast Growth Factor 2 - physiology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Integrin alphaVbeta3 - physiology</subject><subject>MAP Kinase Signaling System - physiology</subject><subject>Mitogen-Activated Protein Kinase 1 - physiology</subject><subject>Mitogen-Activated Protein Kinase 3 - physiology</subject><subject>Neovascularization, Physiologic - drug effects</subject><subject>Propionates - pharmacology</subject><subject>Thyroxine - analogs & derivatives</subject><subject>Thyroxine - pharmacology</subject><subject>Vertebrates: endocrinology</subject><issn>0013-7227</issn><issn>1945-7170</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><recordid>eNpt0UFrHCEUB3ApLc026a3n4qWlhUyqozPOHJdNmyykJNDtWd7qm41hVjfqHPI9-oHrZhdyCQgi_N5T35-QT5xd8JqzH-gvasaaiouevSEz3sumUlyxt2TGGBeVqmt1Qj6k9FCOUkrxnpzwVnSya-sZ-XcXA_iNCxv0mFyic5Nd8DQMNN8jXd0_xeAsvQ5xGzzSuYcxbKg4b6pL54INeQ92ZZUiZ0p1wd8ul6u7-Xe6THTpXXaQ0VLIzw0XOI70zxQHMEjB2wPKuInO099on_EZeTfAmPDjcT8lf3_9XC2uq5vbq-ViflMZyXiueoYcBayFAaxV3_dNa9dKDBI5V6oDsC12xnS2VkapHtaq54IZ1QwKOEcUp-TroW_5wOOEKeutS6a8EDyGKelWqaZTTBZ4foAmhpQiDnoX3Rbik-ZM71PQ6PU-Bb1PofDPx77Teov2BR_HXsCXI4BkYBwieOPSi1OtbGomihMHh94GU0aEu4gp6YcwxZJEev36_zS4oNM</recordid><startdate>20060401</startdate><enddate>20060401</enddate><creator>Mousa, Shaker A</creator><creator>O’Connor, Laura</creator><creator>Davis, Faith B</creator><creator>Davis, Paul J</creator><general>Endocrine Society</general><scope>IQODW</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>7X8</scope></search><sort><creationdate>20060401</creationdate><title>Proangiogenesis Action of the Thyroid Hormone Analog 3,5-Diiodothyropropionic Acid (DITPA) Is Initiated at the Cell Surface and Is Integrin Mediated</title><author>Mousa, Shaker A ; O’Connor, Laura ; Davis, Faith B ; Davis, Paul J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c401t-90e1e3ab3cae2799956db73f4e11778aad6e8cc8d27c779ab79130c75f7a11ee3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cell Membrane - drug effects</topic><topic>Chick Embryo</topic><topic>Diiodothyronines - pharmacology</topic><topic>Fibroblast Growth Factor 2 - physiology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Integrin alphaVbeta3 - physiology</topic><topic>MAP Kinase Signaling System - physiology</topic><topic>Mitogen-Activated Protein Kinase 1 - physiology</topic><topic>Mitogen-Activated Protein Kinase 3 - physiology</topic><topic>Neovascularization, Physiologic - drug effects</topic><topic>Propionates - pharmacology</topic><topic>Thyroxine - analogs & derivatives</topic><topic>Thyroxine - pharmacology</topic><topic>Vertebrates: endocrinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mousa, Shaker A</creatorcontrib><creatorcontrib>O’Connor, Laura</creatorcontrib><creatorcontrib>Davis, Faith B</creatorcontrib><creatorcontrib>Davis, Paul J</creatorcontrib><collection>Pascal-Francis</collection><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>Endocrinology (Philadelphia)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mousa, Shaker A</au><au>O’Connor, Laura</au><au>Davis, Faith B</au><au>Davis, Paul J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Proangiogenesis Action of the Thyroid Hormone Analog 3,5-Diiodothyropropionic Acid (DITPA) Is Initiated at the Cell Surface and Is Integrin Mediated</atitle><jtitle>Endocrinology (Philadelphia)</jtitle><addtitle>Endocrinology</addtitle><date>2006-04-01</date><risdate>2006</risdate><volume>147</volume><issue>4</issue><spage>1602</spage><epage>1607</epage><pages>1602-1607</pages><issn>0013-7227</issn><eissn>1945-7170</eissn><coden>ENDOAO</coden><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>We have recently described the proangiogenesis effects of thyroid hormone in the chick chorioallantoic membrane (CAM) model. Generation of new blood vessels from existing vessels was promoted 2- to 3-fold by either T4 or T3 at 10−8–10−7 m total hormone concentrations. In the present studies, nanomolar concentrations of 3,5-diiodothyropropionic acid (DITPA), a thyroid hormone analog with inotropic but not chronotropic properties, exhibited potent proangiogenic activity that was comparable to that obtained with T3 and T4 in both the CAM model and in an in vitro three-dimensional human microvascular endothelial sprouting assay. The proangiogenesis effect of DITPA was inhibited by tetraiodothyroacetic acid, a thyroid hormone analog that competes with T4 and T3 for a novel cell surface hormone receptor site on integrin αvβ3. The thyroid hormone analogs DITPA, T4, and T4-agarose, as well as basic fibroblast growth factor (b-FGF) and vascular endothelial cell growth factor, demonstrated comparable proangiogenic effects in the CAM model and in the three-dimensional human microvascular endothelial sprouting model. 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subjects | Animals Biological and medical sciences Cell Membrane - drug effects Chick Embryo Diiodothyronines - pharmacology Fibroblast Growth Factor 2 - physiology Fundamental and applied biological sciences. Psychology Humans Integrin alphaVbeta3 - physiology MAP Kinase Signaling System - physiology Mitogen-Activated Protein Kinase 1 - physiology Mitogen-Activated Protein Kinase 3 - physiology Neovascularization, Physiologic - drug effects Propionates - pharmacology Thyroxine - analogs & derivatives Thyroxine - pharmacology Vertebrates: endocrinology |
title | Proangiogenesis Action of the Thyroid Hormone Analog 3,5-Diiodothyropropionic Acid (DITPA) Is Initiated at the Cell Surface and Is Integrin Mediated |
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