Arteriogenesis induced by intramyocardial vascular endothelial growth factor 165 gene transfer in chronically ischemic pigs
Exogenous vascular endothelial growth factor (VEGF) improves tissue perfusion in large animals and humans with chronic myocardial ischemia. Because tissue perfusion is mainly dependent on the arteriolar tree, we hypothesized that the neovascularizing effect of VEGF should include arteriogenesis, an...
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| Veröffentlicht in: | Human gene therapy 2003-09, Vol.14 (14), p.1307-1318 |
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| creator | CROTTOGINI, Alberto MECKERT, Patricia Cabeza DE LORENZI, Andrea TELAYNA, Juan MELE, Anibal FERNANDEZ, José L MARANGUNICH, Laura CRISCUOLO, Marcelo CAPOGROSSI, Maurizio C LAGUENS, Rubén JANAVEL, Gustavo Vera LASCANO, Elena NEGRONI, Jorge DEL VALLE, Héctor DULBECCO, Eduardo WERBA, Pablo CUNIBERTI, Luis MARTINEZ, Veronica |
| description | Exogenous vascular endothelial growth factor (VEGF) improves tissue perfusion in large animals and humans with chronic myocardial ischemia. Because tissue perfusion is mainly dependent on the arteriolar tree, we hypothesized that the neovascularizing effect of VEGF should include arteriogenesis, an effect not as yet described in large mammalian models of myocardial ischemia. In the present study we investigated the effect of intramyocardial plasmid-mediated human VEGF(165) gene transfer (pVEGF(165)) on the proliferation of vessels with smooth muscle in a pig model of myocardial ischemia. In addition, we assessed the effect of treatment on capillary growth, myocardial perfusion, myocardial function and collateralization. Three weeks after positioning of an Ameroid constrictor (Research Instruments SW, Escondido, CA) in the left circumflex artery, pigs underwent basal perfusion (single-photon emission computed tomography [SPECT] with (99m)Tc-sestamibi) and regional function (echocardiography) studies at rest and under dobutamine stress, and were then randomly assigned to receive transepicardial injection of pVEGF(165) 3.8 mg (n = 8) or placebo (empty plasmid, n = 8). All experimental steps and data analysis were done in a blinded fashion. Five weeks later, pVEGF(165)-treated pigs showed a significantly higher density of small (8-50 microm in diameter) vessels with smooth muscle, higher density of capillaries, and improved myocardial perfusion. These results indicate an arteriogenic effect of VEGF in a large mammalian model of myocardial ischemia and encourage the use of VEGF to promote arteriolar growth in patients with severe coronary artery disease. |
| doi_str_mv | 10.1089/104303403322319390 |
| format | Article |
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Because tissue perfusion is mainly dependent on the arteriolar tree, we hypothesized that the neovascularizing effect of VEGF should include arteriogenesis, an effect not as yet described in large mammalian models of myocardial ischemia. In the present study we investigated the effect of intramyocardial plasmid-mediated human VEGF(165) gene transfer (pVEGF(165)) on the proliferation of vessels with smooth muscle in a pig model of myocardial ischemia. In addition, we assessed the effect of treatment on capillary growth, myocardial perfusion, myocardial function and collateralization. Three weeks after positioning of an Ameroid constrictor (Research Instruments SW, Escondido, CA) in the left circumflex artery, pigs underwent basal perfusion (single-photon emission computed tomography [SPECT] with (99m)Tc-sestamibi) and regional function (echocardiography) studies at rest and under dobutamine stress, and were then randomly assigned to receive transepicardial injection of pVEGF(165) 3.8 mg (n = 8) or placebo (empty plasmid, n = 8). All experimental steps and data analysis were done in a blinded fashion. Five weeks later, pVEGF(165)-treated pigs showed a significantly higher density of small (8-50 microm in diameter) vessels with smooth muscle, higher density of capillaries, and improved myocardial perfusion. These results indicate an arteriogenic effect of VEGF in a large mammalian model of myocardial ischemia and encourage the use of VEGF to promote arteriolar growth in patients with severe coronary artery disease.</description><identifier>ISSN: 1043-0342</identifier><identifier>EISSN: 1557-7422</identifier><identifier>DOI: 10.1089/104303403322319390</identifier><identifier>PMID: 14503966</identifier><identifier>CODEN: HGTHE3</identifier><language>eng</language><publisher>Larchmont, NY: Liebert</publisher><subject>Animals ; Biological and medical sciences ; Biotechnology ; Cardiotonic Agents - pharmacology ; Collateral Circulation - drug effects ; Coronary Angiography ; Coronary Vessels - drug effects ; Disease Models, Animal ; Dobutamine - pharmacology ; Echocardiography ; Fundamental and applied biological sciences. Psychology ; Gene Expression ; Gene therapy ; Gene Transfer Techniques ; Health. Pharmaceutical industry ; Immunohistochemistry ; Industrial applications and implications. Economical aspects ; Myocardial Ischemia - physiopathology ; Myocardial Ischemia - therapy ; Neovascularization, Physiologic - drug effects ; Stress, Physiological - chemically induced ; Swine ; Technetium Tc 99m Sestamibi ; Time Factors ; Tomography, Emission-Computed, Single-Photon ; Transgenes ; vascular endothelial growth factor ; Vascular Endothelial Growth Factor A - administration & dosage ; Vascular Endothelial Growth Factor A - genetics ; Vascular Endothelial Growth Factor A - therapeutic use</subject><ispartof>Human gene therapy, 2003-09, Vol.14 (14), p.1307-1318</ispartof><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c362t-2e337a94481b3fe268a1ca01e29fb4153706405cb0be1d565c109ce5783c3c313</citedby><cites>FETCH-LOGICAL-c362t-2e337a94481b3fe268a1ca01e29fb4153706405cb0be1d565c109ce5783c3c313</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3029,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15164016$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14503966$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>CROTTOGINI, Alberto</creatorcontrib><creatorcontrib>MECKERT, Patricia Cabeza</creatorcontrib><creatorcontrib>DE LORENZI, Andrea</creatorcontrib><creatorcontrib>TELAYNA, Juan</creatorcontrib><creatorcontrib>MELE, Anibal</creatorcontrib><creatorcontrib>FERNANDEZ, José L</creatorcontrib><creatorcontrib>MARANGUNICH, Laura</creatorcontrib><creatorcontrib>CRISCUOLO, Marcelo</creatorcontrib><creatorcontrib>CAPOGROSSI, Maurizio C</creatorcontrib><creatorcontrib>LAGUENS, Rubén</creatorcontrib><creatorcontrib>JANAVEL, Gustavo Vera</creatorcontrib><creatorcontrib>LASCANO, Elena</creatorcontrib><creatorcontrib>NEGRONI, Jorge</creatorcontrib><creatorcontrib>DEL VALLE, Héctor</creatorcontrib><creatorcontrib>DULBECCO, Eduardo</creatorcontrib><creatorcontrib>WERBA, Pablo</creatorcontrib><creatorcontrib>CUNIBERTI, Luis</creatorcontrib><creatorcontrib>MARTINEZ, Veronica</creatorcontrib><title>Arteriogenesis induced by intramyocardial vascular endothelial growth factor 165 gene transfer in chronically ischemic pigs</title><title>Human gene therapy</title><addtitle>Hum Gene Ther</addtitle><description>Exogenous vascular endothelial growth factor (VEGF) improves tissue perfusion in large animals and humans with chronic myocardial ischemia. Because tissue perfusion is mainly dependent on the arteriolar tree, we hypothesized that the neovascularizing effect of VEGF should include arteriogenesis, an effect not as yet described in large mammalian models of myocardial ischemia. In the present study we investigated the effect of intramyocardial plasmid-mediated human VEGF(165) gene transfer (pVEGF(165)) on the proliferation of vessels with smooth muscle in a pig model of myocardial ischemia. In addition, we assessed the effect of treatment on capillary growth, myocardial perfusion, myocardial function and collateralization. Three weeks after positioning of an Ameroid constrictor (Research Instruments SW, Escondido, CA) in the left circumflex artery, pigs underwent basal perfusion (single-photon emission computed tomography [SPECT] with (99m)Tc-sestamibi) and regional function (echocardiography) studies at rest and under dobutamine stress, and were then randomly assigned to receive transepicardial injection of pVEGF(165) 3.8 mg (n = 8) or placebo (empty plasmid, n = 8). All experimental steps and data analysis were done in a blinded fashion. Five weeks later, pVEGF(165)-treated pigs showed a significantly higher density of small (8-50 microm in diameter) vessels with smooth muscle, higher density of capillaries, and improved myocardial perfusion. These results indicate an arteriogenic effect of VEGF in a large mammalian model of myocardial ischemia and encourage the use of VEGF to promote arteriolar growth in patients with severe coronary artery disease.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Biotechnology</subject><subject>Cardiotonic Agents - pharmacology</subject><subject>Collateral Circulation - drug effects</subject><subject>Coronary Angiography</subject><subject>Coronary Vessels - drug effects</subject><subject>Disease Models, Animal</subject><subject>Dobutamine - pharmacology</subject><subject>Echocardiography</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression</subject><subject>Gene therapy</subject><subject>Gene Transfer Techniques</subject><subject>Health. Pharmaceutical industry</subject><subject>Immunohistochemistry</subject><subject>Industrial applications and implications. Economical aspects</subject><subject>Myocardial Ischemia - physiopathology</subject><subject>Myocardial Ischemia - therapy</subject><subject>Neovascularization, Physiologic - drug effects</subject><subject>Stress, Physiological - chemically induced</subject><subject>Swine</subject><subject>Technetium Tc 99m Sestamibi</subject><subject>Time Factors</subject><subject>Tomography, Emission-Computed, Single-Photon</subject><subject>Transgenes</subject><subject>vascular endothelial growth factor</subject><subject>Vascular Endothelial Growth Factor A - administration & dosage</subject><subject>Vascular Endothelial Growth Factor A - genetics</subject><subject>Vascular Endothelial Growth Factor A - therapeutic use</subject><issn>1043-0342</issn><issn>1557-7422</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1r3DAQhkVoyVf7B3IoujQ3NxqNJa2PISRtINBLcjayPN5VkK2tZCcs_fPRkoUceig6aBDP-zCaYewCxA8Qq-YKRI0Ca4EoJUKDjThip6CUqUwt5adSF6AqhDxhZzk_CwGotDlmJ1ArgY3Wp-zvdZop-bimibLP3E_94qjn3a6Uc7LjLjqbem8Df7HZLcEmTlMf5w2F_eM6xdd5wwfr5pg4aMX3Jl6SUx4oFQl3mxQn72wIxZndhkbv-Nav8xf2ebAh09fDfc6e7m4fb35VD79_3t9cP1QOtZwrSYjGNnW9gg4HknplwVkBJJuhq0GhEboWynWiI-iVVg5E40iZFbpyAM_Z5bt3m-KfhfLcjqUPCsFOFJfcGmUEKGn-C0IDiFrtjfIddCnmnGhot8mPNu1aEO1-N-2_uymhbwf70o3Uf0QOyyjA9wNQJm3DUGbofP7gFJR_gsY3vlWXQA</recordid><startdate>20030920</startdate><enddate>20030920</enddate><creator>CROTTOGINI, Alberto</creator><creator>MECKERT, Patricia Cabeza</creator><creator>DE LORENZI, Andrea</creator><creator>TELAYNA, Juan</creator><creator>MELE, Anibal</creator><creator>FERNANDEZ, José L</creator><creator>MARANGUNICH, Laura</creator><creator>CRISCUOLO, Marcelo</creator><creator>CAPOGROSSI, Maurizio C</creator><creator>LAGUENS, Rubén</creator><creator>JANAVEL, Gustavo Vera</creator><creator>LASCANO, Elena</creator><creator>NEGRONI, Jorge</creator><creator>DEL VALLE, Héctor</creator><creator>DULBECCO, Eduardo</creator><creator>WERBA, Pablo</creator><creator>CUNIBERTI, Luis</creator><creator>MARTINEZ, Veronica</creator><general>Liebert</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>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20030920</creationdate><title>Arteriogenesis induced by intramyocardial vascular endothelial growth factor 165 gene transfer in chronically ischemic pigs</title><author>CROTTOGINI, Alberto ; MECKERT, Patricia Cabeza ; DE LORENZI, Andrea ; TELAYNA, Juan ; MELE, Anibal ; FERNANDEZ, José L ; MARANGUNICH, Laura ; CRISCUOLO, Marcelo ; CAPOGROSSI, Maurizio C ; LAGUENS, Rubén ; JANAVEL, Gustavo Vera ; LASCANO, Elena ; NEGRONI, Jorge ; DEL VALLE, Héctor ; DULBECCO, Eduardo ; WERBA, Pablo ; CUNIBERTI, Luis ; MARTINEZ, Veronica</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c362t-2e337a94481b3fe268a1ca01e29fb4153706405cb0be1d565c109ce5783c3c313</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Biotechnology</topic><topic>Cardiotonic Agents - pharmacology</topic><topic>Collateral Circulation - drug effects</topic><topic>Coronary Angiography</topic><topic>Coronary Vessels - drug effects</topic><topic>Disease Models, Animal</topic><topic>Dobutamine - pharmacology</topic><topic>Echocardiography</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression</topic><topic>Gene therapy</topic><topic>Gene Transfer Techniques</topic><topic>Health. Pharmaceutical industry</topic><topic>Immunohistochemistry</topic><topic>Industrial applications and implications. Economical aspects</topic><topic>Myocardial Ischemia - physiopathology</topic><topic>Myocardial Ischemia - therapy</topic><topic>Neovascularization, Physiologic - drug effects</topic><topic>Stress, Physiological - chemically induced</topic><topic>Swine</topic><topic>Technetium Tc 99m Sestamibi</topic><topic>Time Factors</topic><topic>Tomography, Emission-Computed, Single-Photon</topic><topic>Transgenes</topic><topic>vascular endothelial growth factor</topic><topic>Vascular Endothelial Growth Factor A - administration & dosage</topic><topic>Vascular Endothelial Growth Factor A - genetics</topic><topic>Vascular Endothelial Growth Factor A - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>CROTTOGINI, Alberto</creatorcontrib><creatorcontrib>MECKERT, Patricia Cabeza</creatorcontrib><creatorcontrib>DE LORENZI, Andrea</creatorcontrib><creatorcontrib>TELAYNA, Juan</creatorcontrib><creatorcontrib>MELE, Anibal</creatorcontrib><creatorcontrib>FERNANDEZ, José L</creatorcontrib><creatorcontrib>MARANGUNICH, Laura</creatorcontrib><creatorcontrib>CRISCUOLO, Marcelo</creatorcontrib><creatorcontrib>CAPOGROSSI, Maurizio C</creatorcontrib><creatorcontrib>LAGUENS, Rubén</creatorcontrib><creatorcontrib>JANAVEL, Gustavo Vera</creatorcontrib><creatorcontrib>LASCANO, Elena</creatorcontrib><creatorcontrib>NEGRONI, Jorge</creatorcontrib><creatorcontrib>DEL VALLE, Héctor</creatorcontrib><creatorcontrib>DULBECCO, Eduardo</creatorcontrib><creatorcontrib>WERBA, Pablo</creatorcontrib><creatorcontrib>CUNIBERTI, Luis</creatorcontrib><creatorcontrib>MARTINEZ, Veronica</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>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Human gene therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>CROTTOGINI, Alberto</au><au>MECKERT, Patricia Cabeza</au><au>DE LORENZI, Andrea</au><au>TELAYNA, Juan</au><au>MELE, Anibal</au><au>FERNANDEZ, José L</au><au>MARANGUNICH, Laura</au><au>CRISCUOLO, Marcelo</au><au>CAPOGROSSI, Maurizio C</au><au>LAGUENS, Rubén</au><au>JANAVEL, Gustavo Vera</au><au>LASCANO, Elena</au><au>NEGRONI, Jorge</au><au>DEL VALLE, Héctor</au><au>DULBECCO, Eduardo</au><au>WERBA, Pablo</au><au>CUNIBERTI, Luis</au><au>MARTINEZ, Veronica</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Arteriogenesis induced by intramyocardial vascular endothelial growth factor 165 gene transfer in chronically ischemic pigs</atitle><jtitle>Human gene therapy</jtitle><addtitle>Hum Gene Ther</addtitle><date>2003-09-20</date><risdate>2003</risdate><volume>14</volume><issue>14</issue><spage>1307</spage><epage>1318</epage><pages>1307-1318</pages><issn>1043-0342</issn><eissn>1557-7422</eissn><coden>HGTHE3</coden><abstract>Exogenous vascular endothelial growth factor (VEGF) improves tissue perfusion in large animals and humans with chronic myocardial ischemia. Because tissue perfusion is mainly dependent on the arteriolar tree, we hypothesized that the neovascularizing effect of VEGF should include arteriogenesis, an effect not as yet described in large mammalian models of myocardial ischemia. In the present study we investigated the effect of intramyocardial plasmid-mediated human VEGF(165) gene transfer (pVEGF(165)) on the proliferation of vessels with smooth muscle in a pig model of myocardial ischemia. In addition, we assessed the effect of treatment on capillary growth, myocardial perfusion, myocardial function and collateralization. Three weeks after positioning of an Ameroid constrictor (Research Instruments SW, Escondido, CA) in the left circumflex artery, pigs underwent basal perfusion (single-photon emission computed tomography [SPECT] with (99m)Tc-sestamibi) and regional function (echocardiography) studies at rest and under dobutamine stress, and were then randomly assigned to receive transepicardial injection of pVEGF(165) 3.8 mg (n = 8) or placebo (empty plasmid, n = 8). All experimental steps and data analysis were done in a blinded fashion. Five weeks later, pVEGF(165)-treated pigs showed a significantly higher density of small (8-50 microm in diameter) vessels with smooth muscle, higher density of capillaries, and improved myocardial perfusion. These results indicate an arteriogenic effect of VEGF in a large mammalian model of myocardial ischemia and encourage the use of VEGF to promote arteriolar growth in patients with severe coronary artery disease.</abstract><cop>Larchmont, NY</cop><pub>Liebert</pub><pmid>14503966</pmid><doi>10.1089/104303403322319390</doi><tpages>12</tpages></addata></record> |
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| ispartof | Human gene therapy, 2003-09, Vol.14 (14), p.1307-1318 |
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| subjects | Animals Biological and medical sciences Biotechnology Cardiotonic Agents - pharmacology Collateral Circulation - drug effects Coronary Angiography Coronary Vessels - drug effects Disease Models, Animal Dobutamine - pharmacology Echocardiography Fundamental and applied biological sciences. Psychology Gene Expression Gene therapy Gene Transfer Techniques Health. Pharmaceutical industry Immunohistochemistry Industrial applications and implications. Economical aspects Myocardial Ischemia - physiopathology Myocardial Ischemia - therapy Neovascularization, Physiologic - drug effects Stress, Physiological - chemically induced Swine Technetium Tc 99m Sestamibi Time Factors Tomography, Emission-Computed, Single-Photon Transgenes vascular endothelial growth factor Vascular Endothelial Growth Factor A - administration & dosage Vascular Endothelial Growth Factor A - genetics Vascular Endothelial Growth Factor A - therapeutic use |
| title | Arteriogenesis induced by intramyocardial vascular endothelial growth factor 165 gene transfer in chronically ischemic pigs |
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