Beta-Adrenoceptor Blockade Markedly Attenuates Transgene Expression From Cytomegalovirus Promoters Within the Cardiovascular System
OBJECTIVES—The major immediate–early cytomegalovirus enhancer/promoter (MIECMV), widely used in cardiovascular gene therapy, contains several positively regulatory cAMP response elements (CRE). Catecholamine signaling via β-adrenoceptors might increase transgene expression from MIECMV, and if so, β-...
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| Veröffentlicht in: | Arteriosclerosis, thrombosis, and vascular biology thrombosis, and vascular biology, 2006-10, Vol.26 (10), p.2267-2274 |
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| container_title | Arteriosclerosis, thrombosis, and vascular biology |
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| creator | Salem, Husein K Ranjzad, Parisa Driessen, Anita Appleby, Clare E Heagerty, Anthony M Kingston, Paul A |
| description | OBJECTIVES—The major immediate–early cytomegalovirus enhancer/promoter (MIECMV), widely used in cardiovascular gene therapy, contains several positively regulatory cAMP response elements (CRE). Catecholamine signaling via β-adrenoceptors might increase transgene expression from MIECMV, and if so, β-blockers may have a detrimental effect on the efficacy of clinical cardiovascular gene therapy strategies.
METHODS AND RESULTS—Cultured smooth muscle cells were exposed to isoprenaline, atenolol, or propranolol, alone and in combination before infection with adenoviruses expressing β-galactosidase. β-galactosidase expression was assayed 72 hours later. Isoprenaline increased transgene expression from MIECMV up to 8-fold (P |
| doi_str_mv | 10.1161/01.ATV.0000239445.67579.19 |
| format | Article |
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METHODS AND RESULTS—Cultured smooth muscle cells were exposed to isoprenaline, atenolol, or propranolol, alone and in combination before infection with adenoviruses expressing β-galactosidase. β-galactosidase expression was assayed 72 hours later. Isoprenaline increased transgene expression from MIECMV up to 8-fold (P<0.001), but had no effect on a promoter containing no CRE. The effect of isoprenaline was inhibited by β-blockade and by specific CRE-decoy oligonucleotides. β-blockers did not reduce transgene expression below basal levels. After adenovirus-mediated porcine intracoronary gene transfer, however, β-blockade reduced β-galactosidase expression by up to 250-fold compared with non-β-blocked animals (P<0.01).
CONCLUSIONS—Enhancement of promoter activity by endogenous catecholamines is essential for high-level transgene expression from MIECMV within the vasculature. β-blocker-mediated suppression of transgene expression from MIECMV in vascular tissues has a significant bearing on clinical studies of cardiovascular gene transfer. This is the first described interaction to our knowledge between widely prescribed pharmaceuticals and a commonly used promoter of clinical transgene expression.</description><identifier>ISSN: 1079-5642</identifier><identifier>EISSN: 1524-4636</identifier><identifier>DOI: 10.1161/01.ATV.0000239445.67579.19</identifier><identifier>PMID: 16888240</identifier><identifier>CODEN: ATVBFA</identifier><language>eng</language><publisher>Philadelphia, PA: American Heart Association, Inc</publisher><subject>Adrenergic beta-Antagonists - pharmacology ; Animals ; Atherosclerosis (general aspects, experimental research) ; Biological and medical sciences ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Cells, Cultured ; Coronary Vessels - cytology ; Coronary Vessels - metabolism ; Cyclic AMP Response Element-Binding Protein - physiology ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; Fundamental and applied biological sciences. Psychology ; Gene Expression - drug effects ; Gene Transfer Techniques ; Genetic Vectors ; Humans ; Isoproterenol - pharmacology ; Lymphatic system ; Medical sciences ; Muromegalovirus - genetics ; Myocytes, Smooth Muscle - metabolism ; Neuropharmacology ; Pharmacology. Drug treatments ; Promoter Regions, Genetic ; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) ; Psychology. Psychoanalysis. Psychiatry ; Psychopharmacology ; Swine ; Transgenes ; Vertebrates: cardiovascular system</subject><ispartof>Arteriosclerosis, thrombosis, and vascular biology, 2006-10, Vol.26 (10), p.2267-2274</ispartof><rights>2006 American Heart Association, Inc.</rights><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4797-87a7e767c9d8f877c1d0ef12bbb570b473379edad149859ca1396797b717f4ac3</citedby><cites>FETCH-LOGICAL-c4797-87a7e767c9d8f877c1d0ef12bbb570b473379edad149859ca1396797b717f4ac3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,27907,27908</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18168785$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16888240$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Salem, Husein K</creatorcontrib><creatorcontrib>Ranjzad, Parisa</creatorcontrib><creatorcontrib>Driessen, Anita</creatorcontrib><creatorcontrib>Appleby, Clare E</creatorcontrib><creatorcontrib>Heagerty, Anthony M</creatorcontrib><creatorcontrib>Kingston, Paul A</creatorcontrib><title>Beta-Adrenoceptor Blockade Markedly Attenuates Transgene Expression From Cytomegalovirus Promoters Within the Cardiovascular System</title><title>Arteriosclerosis, thrombosis, and vascular biology</title><addtitle>Arterioscler Thromb Vasc Biol</addtitle><description>OBJECTIVES—The major immediate–early cytomegalovirus enhancer/promoter (MIECMV), widely used in cardiovascular gene therapy, contains several positively regulatory cAMP response elements (CRE). Catecholamine signaling via β-adrenoceptors might increase transgene expression from MIECMV, and if so, β-blockers may have a detrimental effect on the efficacy of clinical cardiovascular gene therapy strategies.
METHODS AND RESULTS—Cultured smooth muscle cells were exposed to isoprenaline, atenolol, or propranolol, alone and in combination before infection with adenoviruses expressing β-galactosidase. β-galactosidase expression was assayed 72 hours later. Isoprenaline increased transgene expression from MIECMV up to 8-fold (P<0.001), but had no effect on a promoter containing no CRE. The effect of isoprenaline was inhibited by β-blockade and by specific CRE-decoy oligonucleotides. β-blockers did not reduce transgene expression below basal levels. After adenovirus-mediated porcine intracoronary gene transfer, however, β-blockade reduced β-galactosidase expression by up to 250-fold compared with non-β-blocked animals (P<0.01).
CONCLUSIONS—Enhancement of promoter activity by endogenous catecholamines is essential for high-level transgene expression from MIECMV within the vasculature. β-blocker-mediated suppression of transgene expression from MIECMV in vascular tissues has a significant bearing on clinical studies of cardiovascular gene transfer. This is the first described interaction to our knowledge between widely prescribed pharmaceuticals and a commonly used promoter of clinical transgene expression.</description><subject>Adrenergic beta-Antagonists - pharmacology</subject><subject>Animals</subject><subject>Atherosclerosis (general aspects, experimental research)</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Cardiology. Vascular system</subject><subject>Cells, Cultured</subject><subject>Coronary Vessels - cytology</subject><subject>Coronary Vessels - metabolism</subject><subject>Cyclic AMP Response Element-Binding Protein - physiology</subject><subject>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression - drug effects</subject><subject>Gene Transfer Techniques</subject><subject>Genetic Vectors</subject><subject>Humans</subject><subject>Isoproterenol - pharmacology</subject><subject>Lymphatic system</subject><subject>Medical sciences</subject><subject>Muromegalovirus - genetics</subject><subject>Myocytes, Smooth Muscle - metabolism</subject><subject>Neuropharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Promoter Regions, Genetic</subject><subject>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopharmacology</subject><subject>Swine</subject><subject>Transgenes</subject><subject>Vertebrates: cardiovascular system</subject><issn>1079-5642</issn><issn>1524-4636</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkVFv0zAUhSMEYmPwF5CFBG8JduL4xrx11caQhkCiwKPlODdrqBMX29noM3987lqplixfWd-59-qcLHvHaMGYYB8pKxarXwVNp6wk53UhoAZZMPksO2d1yXMuKvE81RRkXgtenmWvQviTeF6W9GV2xkTTNCWn59n_S4w6X3QeJ2dwG50nl9aZje6QfNV-g53dkUWMOM06YiArr6dwhxOSq39bjyEMbiLX3o1kuYtuxDtt3f3g50C-p08X0Qfye4jrYSJxjWSpfTe4ex3MbLUnP3Yh4vg6e9FrG_DN8b3Ifl5frZY3-e23z1-Wi9vccJCQN6ABQYCRXdM3AIZ1FHtWtm1bA205VBVI7HTHuGxqaTSrpEjCFhj0XJvqIvtw6Lv17u-MIapxCAat1RO6OagnU6CqE_jpABrvQvDYq60fRu13ilG1j0BRplIE6hSBeopAMZnEb49T5nbE7iQ9ep6A90cg2aBtnxw1QzhxTSKh2W_BD9yDs3sfN3Z-QK_WqG1c70fzStA6LykVbL9Ini6D6hFc56IL</recordid><startdate>200610</startdate><enddate>200610</enddate><creator>Salem, Husein K</creator><creator>Ranjzad, Parisa</creator><creator>Driessen, Anita</creator><creator>Appleby, Clare E</creator><creator>Heagerty, Anthony M</creator><creator>Kingston, Paul A</creator><general>American Heart Association, Inc</general><general>Lippincott</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>200610</creationdate><title>Beta-Adrenoceptor Blockade Markedly Attenuates Transgene Expression From Cytomegalovirus Promoters Within the Cardiovascular System</title><author>Salem, Husein K ; Ranjzad, Parisa ; Driessen, Anita ; Appleby, Clare E ; Heagerty, Anthony M ; Kingston, Paul A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4797-87a7e767c9d8f877c1d0ef12bbb570b473379edad149859ca1396797b717f4ac3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Adrenergic beta-Antagonists - pharmacology</topic><topic>Animals</topic><topic>Atherosclerosis (general aspects, experimental research)</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Cardiology. Vascular system</topic><topic>Cells, Cultured</topic><topic>Coronary Vessels - cytology</topic><topic>Coronary Vessels - metabolism</topic><topic>Cyclic AMP Response Element-Binding Protein - physiology</topic><topic>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression - drug effects</topic><topic>Gene Transfer Techniques</topic><topic>Genetic Vectors</topic><topic>Humans</topic><topic>Isoproterenol - pharmacology</topic><topic>Lymphatic system</topic><topic>Medical sciences</topic><topic>Muromegalovirus - genetics</topic><topic>Myocytes, Smooth Muscle - metabolism</topic><topic>Neuropharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Promoter Regions, Genetic</topic><topic>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopharmacology</topic><topic>Swine</topic><topic>Transgenes</topic><topic>Vertebrates: cardiovascular system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Salem, Husein K</creatorcontrib><creatorcontrib>Ranjzad, Parisa</creatorcontrib><creatorcontrib>Driessen, Anita</creatorcontrib><creatorcontrib>Appleby, Clare E</creatorcontrib><creatorcontrib>Heagerty, Anthony M</creatorcontrib><creatorcontrib>Kingston, Paul A</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>Arteriosclerosis, thrombosis, and vascular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Salem, Husein K</au><au>Ranjzad, Parisa</au><au>Driessen, Anita</au><au>Appleby, Clare E</au><au>Heagerty, Anthony M</au><au>Kingston, Paul A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Beta-Adrenoceptor Blockade Markedly Attenuates Transgene Expression From Cytomegalovirus Promoters Within the Cardiovascular System</atitle><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle><addtitle>Arterioscler Thromb Vasc Biol</addtitle><date>2006-10</date><risdate>2006</risdate><volume>26</volume><issue>10</issue><spage>2267</spage><epage>2274</epage><pages>2267-2274</pages><issn>1079-5642</issn><eissn>1524-4636</eissn><coden>ATVBFA</coden><abstract>OBJECTIVES—The major immediate–early cytomegalovirus enhancer/promoter (MIECMV), widely used in cardiovascular gene therapy, contains several positively regulatory cAMP response elements (CRE). Catecholamine signaling via β-adrenoceptors might increase transgene expression from MIECMV, and if so, β-blockers may have a detrimental effect on the efficacy of clinical cardiovascular gene therapy strategies.
METHODS AND RESULTS—Cultured smooth muscle cells were exposed to isoprenaline, atenolol, or propranolol, alone and in combination before infection with adenoviruses expressing β-galactosidase. β-galactosidase expression was assayed 72 hours later. Isoprenaline increased transgene expression from MIECMV up to 8-fold (P<0.001), but had no effect on a promoter containing no CRE. The effect of isoprenaline was inhibited by β-blockade and by specific CRE-decoy oligonucleotides. β-blockers did not reduce transgene expression below basal levels. After adenovirus-mediated porcine intracoronary gene transfer, however, β-blockade reduced β-galactosidase expression by up to 250-fold compared with non-β-blocked animals (P<0.01).
CONCLUSIONS—Enhancement of promoter activity by endogenous catecholamines is essential for high-level transgene expression from MIECMV within the vasculature. β-blocker-mediated suppression of transgene expression from MIECMV in vascular tissues has a significant bearing on clinical studies of cardiovascular gene transfer. This is the first described interaction to our knowledge between widely prescribed pharmaceuticals and a commonly used promoter of clinical transgene expression.</abstract><cop>Philadelphia, PA</cop><cop>Hagerstown, MD</cop><pub>American Heart Association, Inc</pub><pmid>16888240</pmid><doi>10.1161/01.ATV.0000239445.67579.19</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adrenergic beta-Antagonists - pharmacology Animals Atherosclerosis (general aspects, experimental research) Biological and medical sciences Blood and lymphatic vessels Cardiology. Vascular system Cells, Cultured Coronary Vessels - cytology Coronary Vessels - metabolism Cyclic AMP Response Element-Binding Protein - physiology Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous Fundamental and applied biological sciences. Psychology Gene Expression - drug effects Gene Transfer Techniques Genetic Vectors Humans Isoproterenol - pharmacology Lymphatic system Medical sciences Muromegalovirus - genetics Myocytes, Smooth Muscle - metabolism Neuropharmacology Pharmacology. Drug treatments Promoter Regions, Genetic Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) Psychology. Psychoanalysis. Psychiatry Psychopharmacology Swine Transgenes Vertebrates: cardiovascular system |
| title | Beta-Adrenoceptor Blockade Markedly Attenuates Transgene Expression From Cytomegalovirus Promoters Within the Cardiovascular System |
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