Endothelial Nitric Oxide Synthase Gene Transfer Inhibits Human Smooth Muscle Cell Migration via Inhibition of Rho A
Smooth muscle cell (SMC) migration contributes to vascular remodeling. Nitric oxide (NO) produced via endothelial NO synthase (eNOS) inhibits SMC migration. This study analyzes signal transduction mechanisms of SMC migration targeted by NO. SMCs were cultured from human saphenous veins, and cell mig...
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| Veröffentlicht in: | Journal of cardiovascular pharmacology 2008-10, Vol.52 (4), p.369-374 |
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| creator | Largiadèr, Thomas Eto, Masato Payeli, Sravan K Greutert, Helen Viswambharan, Hema Lachat, Mario Zünd, Gregor Yang, Zhihong Tanner, Felix C Lüscher, Thomas F |
| description | Smooth muscle cell (SMC) migration contributes to vascular remodeling. Nitric oxide (NO) produced via endothelial NO synthase (eNOS) inhibits SMC migration. This study analyzes signal transduction mechanisms of SMC migration targeted by NO. SMCs were cultured from human saphenous veins, and cell migration was studied using Boyden chambers. PDGF-BB (0.1 to 10 ng/ml) stimulated SMC migration in a concentration-dependent manner, which was inhibited by adenoviral-mediated overexpression of eNOS and by the NO donor diethylentriamine NONOate (DETANO, 10 to 10 mol/L). NO release was enhanced in eNOS-transduced SMCs, and L-NAME blunted the effect of eNOS overexpression on migration. PDGF-BB (10 ng/ml) activated Rho A, which was inhibited by the overexpression of eNOS by DETANO and by 8 bromo-cGMP. The inhibitory effect of DETANO on Rho A activity was prevented by the cGMP-dependant kinase inhibitor. Furthermore, inhibition of Rho A by C3 exoenzyme and inhibition of ROCK by Y-27632 diminished cell migration stimulated by PDGF-BB. Finally, in the cells overexpressing constitutively active ROCK mutant (CAT), DETANO failed to prevent PDGF-BB-induced SMC migration. In conclusion, NO inhibits human SMC migration via blockade of the Rho A pathway. |
| doi_str_mv | 10.1097/FJC.0b013e31818953d0 |
| format | Article |
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Nitric oxide (NO) produced via endothelial NO synthase (eNOS) inhibits SMC migration. This study analyzes signal transduction mechanisms of SMC migration targeted by NO. SMCs were cultured from human saphenous veins, and cell migration was studied using Boyden chambers. PDGF-BB (0.1 to 10 ng/ml) stimulated SMC migration in a concentration-dependent manner, which was inhibited by adenoviral-mediated overexpression of eNOS and by the NO donor diethylentriamine NONOate (DETANO, 10 to 10 mol/L). NO release was enhanced in eNOS-transduced SMCs, and L-NAME blunted the effect of eNOS overexpression on migration. PDGF-BB (10 ng/ml) activated Rho A, which was inhibited by the overexpression of eNOS by DETANO and by 8 bromo-cGMP. The inhibitory effect of DETANO on Rho A activity was prevented by the cGMP-dependant kinase inhibitor. Furthermore, inhibition of Rho A by C3 exoenzyme and inhibition of ROCK by Y-27632 diminished cell migration stimulated by PDGF-BB. Finally, in the cells overexpressing constitutively active ROCK mutant (CAT), DETANO failed to prevent PDGF-BB-induced SMC migration. In conclusion, NO inhibits human SMC migration via blockade of the Rho A pathway.</description><identifier>ISSN: 0160-2446</identifier><identifier>EISSN: 1533-4023</identifier><identifier>DOI: 10.1097/FJC.0b013e31818953d0</identifier><identifier>PMID: 18841072</identifier><language>eng</language><publisher>United States: Lippincott Williams & Wilkins, Inc</publisher><subject>Adenoviridae - genetics ; Cell Movement - genetics ; Cell Movement - physiology ; Cells, Cultured ; Culture Media, Serum-Free ; Dose-Response Relationship, Drug ; Enzyme Activation - drug effects ; Gene Expression Regulation, Enzymologic - genetics ; Gene Transfer Techniques ; Humans ; Muscle, Smooth, Vascular - cytology ; Muscle, Smooth, Vascular - metabolism ; Nitric Oxide Donors - pharmacology ; Nitric Oxide Synthase Type III - genetics ; Platelet-Derived Growth Factor - pharmacology ; Proto-Oncogene Proteins c-sis ; rho-Associated Kinases - antagonists & inhibitors ; Saphenous Vein - cytology</subject><ispartof>Journal of cardiovascular pharmacology, 2008-10, Vol.52 (4), p.369-374</ispartof><rights>2008 Lippincott Williams & Wilkins, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4660-82c533241ee58837ff473ed78c02bb52d95c592e42608cb773b3b5fd8be5fddb3</citedby><cites>FETCH-LOGICAL-c4660-82c533241ee58837ff473ed78c02bb52d95c592e42608cb773b3b5fd8be5fddb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18841072$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Largiadèr, Thomas</creatorcontrib><creatorcontrib>Eto, Masato</creatorcontrib><creatorcontrib>Payeli, Sravan K</creatorcontrib><creatorcontrib>Greutert, Helen</creatorcontrib><creatorcontrib>Viswambharan, Hema</creatorcontrib><creatorcontrib>Lachat, Mario</creatorcontrib><creatorcontrib>Zünd, Gregor</creatorcontrib><creatorcontrib>Yang, Zhihong</creatorcontrib><creatorcontrib>Tanner, Felix C</creatorcontrib><creatorcontrib>Lüscher, Thomas F</creatorcontrib><title>Endothelial Nitric Oxide Synthase Gene Transfer Inhibits Human Smooth Muscle Cell Migration via Inhibition of Rho A</title><title>Journal of cardiovascular pharmacology</title><addtitle>J Cardiovasc Pharmacol</addtitle><description>Smooth muscle cell (SMC) migration contributes to vascular remodeling. Nitric oxide (NO) produced via endothelial NO synthase (eNOS) inhibits SMC migration. This study analyzes signal transduction mechanisms of SMC migration targeted by NO. SMCs were cultured from human saphenous veins, and cell migration was studied using Boyden chambers. PDGF-BB (0.1 to 10 ng/ml) stimulated SMC migration in a concentration-dependent manner, which was inhibited by adenoviral-mediated overexpression of eNOS and by the NO donor diethylentriamine NONOate (DETANO, 10 to 10 mol/L). NO release was enhanced in eNOS-transduced SMCs, and L-NAME blunted the effect of eNOS overexpression on migration. PDGF-BB (10 ng/ml) activated Rho A, which was inhibited by the overexpression of eNOS by DETANO and by 8 bromo-cGMP. The inhibitory effect of DETANO on Rho A activity was prevented by the cGMP-dependant kinase inhibitor. Furthermore, inhibition of Rho A by C3 exoenzyme and inhibition of ROCK by Y-27632 diminished cell migration stimulated by PDGF-BB. Finally, in the cells overexpressing constitutively active ROCK mutant (CAT), DETANO failed to prevent PDGF-BB-induced SMC migration. In conclusion, NO inhibits human SMC migration via blockade of the Rho A pathway.</description><subject>Adenoviridae - genetics</subject><subject>Cell Movement - genetics</subject><subject>Cell Movement - physiology</subject><subject>Cells, Cultured</subject><subject>Culture Media, Serum-Free</subject><subject>Dose-Response Relationship, Drug</subject><subject>Enzyme Activation - drug effects</subject><subject>Gene Expression Regulation, Enzymologic - genetics</subject><subject>Gene Transfer Techniques</subject><subject>Humans</subject><subject>Muscle, Smooth, Vascular - cytology</subject><subject>Muscle, Smooth, Vascular - metabolism</subject><subject>Nitric Oxide Donors - pharmacology</subject><subject>Nitric Oxide Synthase Type III - genetics</subject><subject>Platelet-Derived Growth Factor - pharmacology</subject><subject>Proto-Oncogene Proteins c-sis</subject><subject>rho-Associated Kinases - antagonists & inhibitors</subject><subject>Saphenous Vein - cytology</subject><issn>0160-2446</issn><issn>1533-4023</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kElP5DAQhS0Egmb5Bwj5xK3Ba-IcUYtVLBLLObKdCjHjxIydDMO_x6gbIXHgUqWSvvf06iG0T8kRJVV5fHa1OCKGUA6cKqoqyRuyhmZUcj4XhPF1NCO0IHMmRLGFtlN6IYQKWRabaIsqJSgp2Qyl06EJYwfeaY9v3RidxXf_XQP44X0YO50An8MA-DHqIbUQ8eXQOePGhC-mXg_4oQ9Zjm-mZD3gBXiPb9xz1KMLA_7n9Bf_eYYW33cBn-yijVb7BHurvYOezk4fFxfz67vzy8XJ9dyKIgdXzOZfmKAAUiletq0oOTSlsoQZI1lTSSsrBoIVRFlTltxwI9tGGcizMXwHHS59X2P4O0Ea694lmyPqAcKU6qIqKl4QmUGxBG0MKUVo69foeh3fa0rqz7LrXHb9s-wsO1j5T6aH5lu0ajcDagm8BT9CTH_89Aax7kD7sfvd-wO5m414</recordid><startdate>200810</startdate><enddate>200810</enddate><creator>Largiadèr, Thomas</creator><creator>Eto, Masato</creator><creator>Payeli, Sravan K</creator><creator>Greutert, Helen</creator><creator>Viswambharan, Hema</creator><creator>Lachat, Mario</creator><creator>Zünd, Gregor</creator><creator>Yang, Zhihong</creator><creator>Tanner, Felix C</creator><creator>Lüscher, Thomas F</creator><general>Lippincott Williams & Wilkins, Inc</general><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>200810</creationdate><title>Endothelial Nitric Oxide Synthase Gene Transfer Inhibits Human Smooth Muscle Cell Migration via Inhibition of Rho A</title><author>Largiadèr, Thomas ; Eto, Masato ; Payeli, Sravan K ; Greutert, Helen ; Viswambharan, Hema ; Lachat, Mario ; Zünd, Gregor ; Yang, Zhihong ; Tanner, Felix C ; Lüscher, Thomas F</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4660-82c533241ee58837ff473ed78c02bb52d95c592e42608cb773b3b5fd8be5fddb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adenoviridae - genetics</topic><topic>Cell Movement - genetics</topic><topic>Cell Movement - physiology</topic><topic>Cells, Cultured</topic><topic>Culture Media, Serum-Free</topic><topic>Dose-Response Relationship, Drug</topic><topic>Enzyme Activation - drug effects</topic><topic>Gene Expression Regulation, Enzymologic - genetics</topic><topic>Gene Transfer Techniques</topic><topic>Humans</topic><topic>Muscle, Smooth, Vascular - cytology</topic><topic>Muscle, Smooth, Vascular - metabolism</topic><topic>Nitric Oxide Donors - pharmacology</topic><topic>Nitric Oxide Synthase Type III - genetics</topic><topic>Platelet-Derived Growth Factor - pharmacology</topic><topic>Proto-Oncogene Proteins c-sis</topic><topic>rho-Associated Kinases - antagonists & inhibitors</topic><topic>Saphenous Vein - cytology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Largiadèr, Thomas</creatorcontrib><creatorcontrib>Eto, Masato</creatorcontrib><creatorcontrib>Payeli, Sravan K</creatorcontrib><creatorcontrib>Greutert, Helen</creatorcontrib><creatorcontrib>Viswambharan, Hema</creatorcontrib><creatorcontrib>Lachat, Mario</creatorcontrib><creatorcontrib>Zünd, Gregor</creatorcontrib><creatorcontrib>Yang, Zhihong</creatorcontrib><creatorcontrib>Tanner, Felix C</creatorcontrib><creatorcontrib>Lüscher, Thomas F</creatorcontrib><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>Journal of cardiovascular pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Largiadèr, Thomas</au><au>Eto, Masato</au><au>Payeli, Sravan K</au><au>Greutert, Helen</au><au>Viswambharan, Hema</au><au>Lachat, Mario</au><au>Zünd, Gregor</au><au>Yang, Zhihong</au><au>Tanner, Felix C</au><au>Lüscher, Thomas F</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Endothelial Nitric Oxide Synthase Gene Transfer Inhibits Human Smooth Muscle Cell Migration via Inhibition of Rho A</atitle><jtitle>Journal of cardiovascular pharmacology</jtitle><addtitle>J Cardiovasc Pharmacol</addtitle><date>2008-10</date><risdate>2008</risdate><volume>52</volume><issue>4</issue><spage>369</spage><epage>374</epage><pages>369-374</pages><issn>0160-2446</issn><eissn>1533-4023</eissn><abstract>Smooth muscle cell (SMC) migration contributes to vascular remodeling. Nitric oxide (NO) produced via endothelial NO synthase (eNOS) inhibits SMC migration. This study analyzes signal transduction mechanisms of SMC migration targeted by NO. SMCs were cultured from human saphenous veins, and cell migration was studied using Boyden chambers. PDGF-BB (0.1 to 10 ng/ml) stimulated SMC migration in a concentration-dependent manner, which was inhibited by adenoviral-mediated overexpression of eNOS and by the NO donor diethylentriamine NONOate (DETANO, 10 to 10 mol/L). NO release was enhanced in eNOS-transduced SMCs, and L-NAME blunted the effect of eNOS overexpression on migration. PDGF-BB (10 ng/ml) activated Rho A, which was inhibited by the overexpression of eNOS by DETANO and by 8 bromo-cGMP. The inhibitory effect of DETANO on Rho A activity was prevented by the cGMP-dependant kinase inhibitor. Furthermore, inhibition of Rho A by C3 exoenzyme and inhibition of ROCK by Y-27632 diminished cell migration stimulated by PDGF-BB. Finally, in the cells overexpressing constitutively active ROCK mutant (CAT), DETANO failed to prevent PDGF-BB-induced SMC migration. In conclusion, NO inhibits human SMC migration via blockade of the Rho A pathway.</abstract><cop>United States</cop><pub>Lippincott Williams & Wilkins, Inc</pub><pmid>18841072</pmid><doi>10.1097/FJC.0b013e31818953d0</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| source | Ovid Lippincott Williams and Wilkins Journal Legacy Archive; MEDLINE; Journals@Ovid Complete; EZB-FREE-00999 freely available EZB journals |
| subjects | Adenoviridae - genetics Cell Movement - genetics Cell Movement - physiology Cells, Cultured Culture Media, Serum-Free Dose-Response Relationship, Drug Enzyme Activation - drug effects Gene Expression Regulation, Enzymologic - genetics Gene Transfer Techniques Humans Muscle, Smooth, Vascular - cytology Muscle, Smooth, Vascular - metabolism Nitric Oxide Donors - pharmacology Nitric Oxide Synthase Type III - genetics Platelet-Derived Growth Factor - pharmacology Proto-Oncogene Proteins c-sis rho-Associated Kinases - antagonists & inhibitors Saphenous Vein - cytology |
| title | Endothelial Nitric Oxide Synthase Gene Transfer Inhibits Human Smooth Muscle Cell Migration via Inhibition of Rho A |
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