Direct intramuscular injection of plasmid DNA encoding angiopoietin-1 but not angiopoietin-2 augments revascularization in the rabbit ischemic hindlimb
Angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) have recently been identified as ligands for the endothelial cell-specific Tie2 receptor. Little is known regarding the impact of these Tie2 ligands on postnatal neovascularization. Accordingly, we tested the hypothesis that gene transfer of plasmid DN...
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| Veröffentlicht in: | Circulation (New York, N.Y.) N.Y.), 1998-11, Vol.98 (19), p.2081-2087 |
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| creator | SHYU, K.-G MANOR, O MAGNER, M YANCOPOULOS, G. D ISNER, J. M |
| description | Angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) have recently been identified as ligands for the endothelial cell-specific Tie2 receptor. Little is known regarding the impact of these Tie2 ligands on postnatal neovascularization. Accordingly, we tested the hypothesis that gene transfer of plasmid DNA encoding Ang1 and Ang2 could modulate collateral vessel development in a rabbit model of hindlimb ischemia.
pAng1* (n=15), pJFE control (no Ang1* insert) (n=9), pAng2 (n=9), pcDNA3 control (no Ang2 insert) (n=10), or saline (n=5) was injected intramuscularly into the rabbit ischemic hindlimb. Collateral vessel development and limb perfusion were assessed before and 30 days after treatment. Calf blood pressure ratio (ischemic to normal hindlimb) was increased 30 days after Ang1* gene transfer versus controls (Ang1*, 0.90+/-0.02; pJFE, 0.76+/-0.05; saline, 0.77+/-0. 03; P |
| doi_str_mv | 10.1161/01.CIR.98.19.2081 |
| format | Article |
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pAng1* (n=15), pJFE control (no Ang1* insert) (n=9), pAng2 (n=9), pcDNA3 control (no Ang2 insert) (n=10), or saline (n=5) was injected intramuscularly into the rabbit ischemic hindlimb. Collateral vessel development and limb perfusion were assessed before and 30 days after treatment. Calf blood pressure ratio (ischemic to normal hindlimb) was increased 30 days after Ang1* gene transfer versus controls (Ang1*, 0.90+/-0.02; pJFE, 0.76+/-0.05; saline, 0.77+/-0. 03; P<0.05). Angiographic score was higher (P<0.05) in the pAng1* group (0.63+/-0.02) than in the pJFE (0.51+/-0.03) or saline (0. 52+/-0.02) group. Maximal (postpapaverine) blood flow in the ischemic limb was higher (P<0.05) after pAng1* (67.8+/-4.9 mL/min) than pJFE (51.2+/-4.4 mL/min) or saline (52.9+/-4.9 mL/min). Capillary density and capillary/muscle fiber ratio (242+/-12/mm2 and 0.89+/-0.06, respectively) were higher (P<0.01) with pAng1* than pJFE (172+/-11/mm2 and 0.64+/-0.05) or saline (166+/-10/mm2 and 0. 67+/-0.05). Neovascularization was not enhanced with pAng2.
Ang1 but not Ang2 gene transfer produces anatomic and physiological evidence of enhanced collateral vessel formation. Ang1 may modulate neovascularization in adult animals and thus represents a feasible therapeutic strategy for patients with tissue ischemia. The role of Ang2 in postnatal neovascularization remains to be clarified.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/01.CIR.98.19.2081</identifier><identifier>PMID: 9808608</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Angiography ; Angiopoietin-1 ; Angiopoietin-2 ; Animals ; Biological and medical sciences ; Blood and lymphatic vessels ; Blood Pressure - physiology ; Cardiology. Vascular system ; Collateral Circulation - drug effects ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; DNA - genetics ; DNA - pharmacology ; Hindlimb - blood supply ; Hindlimb - diagnostic imaging ; Injections, Intramuscular ; Ischemia - diagnostic imaging ; Ischemia - physiopathology ; Medical sciences ; Membrane Glycoproteins - genetics ; Neovascularization, Physiologic - drug effects ; Plasmids - genetics ; Proteins - genetics ; Rabbits ; Regional Blood Flow - drug effects ; Ultrasonography, Interventional</subject><ispartof>Circulation (New York, N.Y.), 1998-11, Vol.98 (19), p.2081-2087</ispartof><rights>1999 INIST-CNRS</rights><rights>Copyright American Heart Association, Inc. Nov 10, 1998</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c437t-e9406c4b93e21bd2dea92f753524fe38ba44fa5de9a84735b1126c681d5a30433</citedby><cites>FETCH-LOGICAL-c437t-e9406c4b93e21bd2dea92f753524fe38ba44fa5de9a84735b1126c681d5a30433</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3687,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1583874$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9808608$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>SHYU, K.-G</creatorcontrib><creatorcontrib>MANOR, O</creatorcontrib><creatorcontrib>MAGNER, M</creatorcontrib><creatorcontrib>YANCOPOULOS, G. D</creatorcontrib><creatorcontrib>ISNER, J. M</creatorcontrib><title>Direct intramuscular injection of plasmid DNA encoding angiopoietin-1 but not angiopoietin-2 augments revascularization in the rabbit ischemic hindlimb</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>Angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) have recently been identified as ligands for the endothelial cell-specific Tie2 receptor. Little is known regarding the impact of these Tie2 ligands on postnatal neovascularization. Accordingly, we tested the hypothesis that gene transfer of plasmid DNA encoding Ang1 and Ang2 could modulate collateral vessel development in a rabbit model of hindlimb ischemia.
pAng1* (n=15), pJFE control (no Ang1* insert) (n=9), pAng2 (n=9), pcDNA3 control (no Ang2 insert) (n=10), or saline (n=5) was injected intramuscularly into the rabbit ischemic hindlimb. Collateral vessel development and limb perfusion were assessed before and 30 days after treatment. Calf blood pressure ratio (ischemic to normal hindlimb) was increased 30 days after Ang1* gene transfer versus controls (Ang1*, 0.90+/-0.02; pJFE, 0.76+/-0.05; saline, 0.77+/-0. 03; P<0.05). Angiographic score was higher (P<0.05) in the pAng1* group (0.63+/-0.02) than in the pJFE (0.51+/-0.03) or saline (0. 52+/-0.02) group. Maximal (postpapaverine) blood flow in the ischemic limb was higher (P<0.05) after pAng1* (67.8+/-4.9 mL/min) than pJFE (51.2+/-4.4 mL/min) or saline (52.9+/-4.9 mL/min). Capillary density and capillary/muscle fiber ratio (242+/-12/mm2 and 0.89+/-0.06, respectively) were higher (P<0.01) with pAng1* than pJFE (172+/-11/mm2 and 0.64+/-0.05) or saline (166+/-10/mm2 and 0. 67+/-0.05). Neovascularization was not enhanced with pAng2.
Ang1 but not Ang2 gene transfer produces anatomic and physiological evidence of enhanced collateral vessel formation. Ang1 may modulate neovascularization in adult animals and thus represents a feasible therapeutic strategy for patients with tissue ischemia. The role of Ang2 in postnatal neovascularization remains to be clarified.</description><subject>Angiography</subject><subject>Angiopoietin-1</subject><subject>Angiopoietin-2</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Blood Pressure - physiology</subject><subject>Cardiology. Vascular system</subject><subject>Collateral Circulation - drug effects</subject><subject>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</subject><subject>DNA - genetics</subject><subject>DNA - pharmacology</subject><subject>Hindlimb - blood supply</subject><subject>Hindlimb - diagnostic imaging</subject><subject>Injections, Intramuscular</subject><subject>Ischemia - diagnostic imaging</subject><subject>Ischemia - physiopathology</subject><subject>Medical sciences</subject><subject>Membrane Glycoproteins - genetics</subject><subject>Neovascularization, Physiologic - drug effects</subject><subject>Plasmids - genetics</subject><subject>Proteins - genetics</subject><subject>Rabbits</subject><subject>Regional Blood Flow - drug effects</subject><subject>Ultrasonography, Interventional</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkduKFDEQhoMo67j6AF4IQcS7blM5dCeXy6yHhUVB9Dqk0-mZDN3JmKSF9UV8XbPOoOhVUVV_fVXUj9BzIC1AB28ItNubz62SLaiWEgkP0AYE5Q0XTD1EG0KIanpG6WP0JOdDTTvWiwt0oSSRHZEb9PPaJ2cL9qEks6zZrrNJNTvUoo8BxwkfZ5MXP-Lrj1fYBRtHH3bYhJ2Px-hd8aEBPKwFh1j-LVNs1t3iQsk4ue_mxPY_zG-wD7jsHU5mGHxdn-3eLd7ivQ_j7JfhKXo0mTm7Z-d4ib6-e_tl-6G5_fT-Znt121jO-tI4xUln-aCYozCMdHRG0akXrD5hckwOhvPJiNEpI3nPxABAO9tJGIVhhDN2iV6fuMcUv60uF73UW9w8m-DimnVPCOtA9VX48j_hIa4p1Ns0rUxBqIQqgpPIpphzcpM-Jr-YdKeB6HvHNAFdHdNKalD63rE68-IMXofFjX8mzhbV_qtzv37QzFMywfr8Fywkkz1nvwAO2qBz</recordid><startdate>19981110</startdate><enddate>19981110</enddate><creator>SHYU, K.-G</creator><creator>MANOR, O</creator><creator>MAGNER, M</creator><creator>YANCOPOULOS, G. D</creator><creator>ISNER, J. M</creator><general>Lippincott Williams & Wilkins</general><general>American Heart Association, Inc</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>K9.</scope><scope>NAPCQ</scope><scope>U9A</scope><scope>7X8</scope></search><sort><creationdate>19981110</creationdate><title>Direct intramuscular injection of plasmid DNA encoding angiopoietin-1 but not angiopoietin-2 augments revascularization in the rabbit ischemic hindlimb</title><author>SHYU, K.-G ; MANOR, O ; MAGNER, M ; YANCOPOULOS, G. D ; ISNER, J. M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c437t-e9406c4b93e21bd2dea92f753524fe38ba44fa5de9a84735b1126c681d5a30433</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Angiography</topic><topic>Angiopoietin-1</topic><topic>Angiopoietin-2</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Blood Pressure - physiology</topic><topic>Cardiology. Vascular system</topic><topic>Collateral Circulation - drug effects</topic><topic>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</topic><topic>DNA - genetics</topic><topic>DNA - pharmacology</topic><topic>Hindlimb - blood supply</topic><topic>Hindlimb - diagnostic imaging</topic><topic>Injections, Intramuscular</topic><topic>Ischemia - diagnostic imaging</topic><topic>Ischemia - physiopathology</topic><topic>Medical sciences</topic><topic>Membrane Glycoproteins - genetics</topic><topic>Neovascularization, Physiologic - drug effects</topic><topic>Plasmids - genetics</topic><topic>Proteins - genetics</topic><topic>Rabbits</topic><topic>Regional Blood Flow - drug effects</topic><topic>Ultrasonography, Interventional</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SHYU, K.-G</creatorcontrib><creatorcontrib>MANOR, O</creatorcontrib><creatorcontrib>MAGNER, M</creatorcontrib><creatorcontrib>YANCOPOULOS, G. D</creatorcontrib><creatorcontrib>ISNER, J. M</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>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</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>SHYU, K.-G</au><au>MANOR, O</au><au>MAGNER, M</au><au>YANCOPOULOS, G. D</au><au>ISNER, J. M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Direct intramuscular injection of plasmid DNA encoding angiopoietin-1 but not angiopoietin-2 augments revascularization in the rabbit ischemic hindlimb</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>1998-11-10</date><risdate>1998</risdate><volume>98</volume><issue>19</issue><spage>2081</spage><epage>2087</epage><pages>2081-2087</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>Angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) have recently been identified as ligands for the endothelial cell-specific Tie2 receptor. Little is known regarding the impact of these Tie2 ligands on postnatal neovascularization. Accordingly, we tested the hypothesis that gene transfer of plasmid DNA encoding Ang1 and Ang2 could modulate collateral vessel development in a rabbit model of hindlimb ischemia.
pAng1* (n=15), pJFE control (no Ang1* insert) (n=9), pAng2 (n=9), pcDNA3 control (no Ang2 insert) (n=10), or saline (n=5) was injected intramuscularly into the rabbit ischemic hindlimb. Collateral vessel development and limb perfusion were assessed before and 30 days after treatment. Calf blood pressure ratio (ischemic to normal hindlimb) was increased 30 days after Ang1* gene transfer versus controls (Ang1*, 0.90+/-0.02; pJFE, 0.76+/-0.05; saline, 0.77+/-0. 03; P<0.05). Angiographic score was higher (P<0.05) in the pAng1* group (0.63+/-0.02) than in the pJFE (0.51+/-0.03) or saline (0. 52+/-0.02) group. Maximal (postpapaverine) blood flow in the ischemic limb was higher (P<0.05) after pAng1* (67.8+/-4.9 mL/min) than pJFE (51.2+/-4.4 mL/min) or saline (52.9+/-4.9 mL/min). Capillary density and capillary/muscle fiber ratio (242+/-12/mm2 and 0.89+/-0.06, respectively) were higher (P<0.01) with pAng1* than pJFE (172+/-11/mm2 and 0.64+/-0.05) or saline (166+/-10/mm2 and 0. 67+/-0.05). Neovascularization was not enhanced with pAng2.
Ang1 but not Ang2 gene transfer produces anatomic and physiological evidence of enhanced collateral vessel formation. Ang1 may modulate neovascularization in adult animals and thus represents a feasible therapeutic strategy for patients with tissue ischemia. The role of Ang2 in postnatal neovascularization remains to be clarified.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>9808608</pmid><doi>10.1161/01.CIR.98.19.2081</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Circulation (New York, N.Y.), 1998-11, Vol.98 (19), p.2081-2087 |
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| source | MEDLINE; EZB Electronic Journals Library; American Heart Association; Journals@Ovid Complete |
| subjects | Angiography Angiopoietin-1 Angiopoietin-2 Animals Biological and medical sciences Blood and lymphatic vessels Blood Pressure - physiology Cardiology. Vascular system Collateral Circulation - drug effects Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous DNA - genetics DNA - pharmacology Hindlimb - blood supply Hindlimb - diagnostic imaging Injections, Intramuscular Ischemia - diagnostic imaging Ischemia - physiopathology Medical sciences Membrane Glycoproteins - genetics Neovascularization, Physiologic - drug effects Plasmids - genetics Proteins - genetics Rabbits Regional Blood Flow - drug effects Ultrasonography, Interventional |
| title | Direct intramuscular injection of plasmid DNA encoding angiopoietin-1 but not angiopoietin-2 augments revascularization in the rabbit ischemic hindlimb |
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