K+ Channels Expression in Hypertension After Arterial Injury, and Effect of Selective Kv1.3 Blockade with PAP-1 on Intimal Hyperplasia Formation
Introduction K + channels are central to vascular pathophysiology. Previous results demonstrated that phenotypic modulation associates with a change in Kv1.3 to Kv1.5 expression, and that Kv1.3 blockade inhibits proliferation of VSMCs cultures. Purpose To explore whether the Kv1.3 to Kv1.5 switch co...
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| Veröffentlicht in: | Cardiovascular drugs and therapy 2014-12, Vol.28 (6), p.501-511 |
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| creator | Cidad, P. Novensà, L. Garabito, M. Batlle, M. Dantas, A. P. Heras, M. López-López, J. R. Pérez-García, M. T. Roqué, M. |
| description | Introduction
K
+
channels are central to vascular pathophysiology. Previous results demonstrated that phenotypic modulation associates with a change in Kv1.3 to Kv1.5 expression, and that Kv1.3 blockade inhibits proliferation of VSMCs cultures.
Purpose
To explore whether the Kv1.3 to Kv1.5 switch could be a marker of the increased risk of intimal hyperplasia in essential hypertension and whether systemic treatment with Kv1.3 blockers can prevent intimal hyperplasia after endoluminal lesion .
Methods
Morphometric and immunohistochemical analysis were performed in arterial segments following arterial injury and constant infusion of the Kv1.3 blocker PAP-1 during 28 days. Differential expression of K
+
channel genes was studied in VSMC from hypertensive (BPH) and normotensive (BPN) mice, both in control and after endoluminal lesion. Finally, the migration and proliferation rate of BPN and BPH VSMCs was explored in vitro.
Results
Changes in mRNA expression led to an increased Kv1.3/Kv1.5 ratio in BPH VSMC. Consistent with this, arterial injury in BPH mice induced a higher degree of luminal stenosis, (84 ± 4 % vs. 70 ± 5 % in BPN,
p
|
| doi_str_mv | 10.1007/s10557-014-6554-5 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1635008562</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1635008562</sourcerecordid><originalsourceid>FETCH-LOGICAL-c487t-e5d70c0d146455fd2f679d80b12eff2a112cff2cbc8f1706e2abd2a4d1ac5e613</originalsourceid><addsrcrecordid>eNp9kc9uEzEQxi0EomnhAbggX5CQiovHa--fY4hSGrUSlYCz5XjHdIPj3dq7hbwFj4zTBLhxGo_8m-_TzEfIK-AXwHn1PgFXqmIcJCuVkkw9ITNQVcEqIeEpmfFGcFYIXp6Q05Q2PM80Tf2cnAhVyLoWckZ-XZ_TxZ0JAX2iy59DxJS6PtAu0KvdgHHE8NjP3YiRznMfO-PpKmymuHtHTWjp0jm0I-0d_Yw-v7oHpNcPcFHQD763302L9Ec33tHb-S0DmrVWYey2WeTRYPAmdYZe9nFrxuz0gjxzxid8eaxn5Ovl8sviit18-rhazG-YlXU1MlRtxS1vQZZSKdcKV1ZNW_M1CHROGABhc7VrWzuoeInCrFthZAvGKiyhOCNvD7pD7O8nTKPedsmi9yZgPyUNZaE4r1UpMgoH1MY-pYhODzEvEHcauN4HoQ9B6ByE3gehVZ55fZSf1lts_078uXwG3hwBk6zxLppgu_SPa7iSUO2FxIFL-St8w6g3_RRDPs1_3H8D9Omg5A</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1635008562</pqid></control><display><type>article</type><title>K+ Channels Expression in Hypertension After Arterial Injury, and Effect of Selective Kv1.3 Blockade with PAP-1 on Intimal Hyperplasia Formation</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><creator>Cidad, P. ; Novensà, L. ; Garabito, M. ; Batlle, M. ; Dantas, A. P. ; Heras, M. ; López-López, J. R. ; Pérez-García, M. T. ; Roqué, M.</creator><creatorcontrib>Cidad, P. ; Novensà, L. ; Garabito, M. ; Batlle, M. ; Dantas, A. P. ; Heras, M. ; López-López, J. R. ; Pérez-García, M. T. ; Roqué, M.</creatorcontrib><description>Introduction
K
+
channels are central to vascular pathophysiology. Previous results demonstrated that phenotypic modulation associates with a change in Kv1.3 to Kv1.5 expression, and that Kv1.3 blockade inhibits proliferation of VSMCs cultures.
Purpose
To explore whether the Kv1.3 to Kv1.5 switch could be a marker of the increased risk of intimal hyperplasia in essential hypertension and whether systemic treatment with Kv1.3 blockers can prevent intimal hyperplasia after endoluminal lesion .
Methods
Morphometric and immunohistochemical analysis were performed in arterial segments following arterial injury and constant infusion of the Kv1.3 blocker PAP-1 during 28 days. Differential expression of K
+
channel genes was studied in VSMC from hypertensive (BPH) and normotensive (BPN) mice, both in control and after endoluminal lesion. Finally, the migration and proliferation rate of BPN and BPH VSMCs was explored in vitro.
Results
Changes in mRNA expression led to an increased Kv1.3/Kv1.5 ratio in BPH VSMC. Consistent with this, arterial injury in BPH mice induced a higher degree of luminal stenosis, (84 ± 4 % vs. 70 ± 5 % in BPN,
p
< 0.01), although no differences in migration and proliferation rate were observed in cultured VSMCs. The in vivo proliferative lesions were significantly decreased upon PAP-1 systemic infusion (18 ± 6 % vs. 58 ± 20 % with vehicle,
p
< 0.05).
Conclusions
Hypertension leads to a higher degree of luminal stenosis in our arterial injury model, that correlates with a decreased expression of Kv1.5 channels. Kv1.3 blockers decreased in vitro VSMCs proliferation, migration, and in vivo intimal hyperplasia formation, pointing to Kv1.3 channels as promising therapeutical targets against restenosis.</description><identifier>ISSN: 0920-3206</identifier><identifier>EISSN: 1573-7241</identifier><identifier>DOI: 10.1007/s10557-014-6554-5</identifier><identifier>PMID: 25348824</identifier><identifier>CODEN: CDTHET</identifier><language>eng</language><publisher>Boston: Springer US</publisher><subject>Animals ; Arterial hypertension. Arterial hypotension ; Arteries - drug effects ; Arteries - metabolism ; Biological and medical sciences ; Blood and lymphatic vessels ; Cardiology ; Cardiology. Vascular system ; Cardiovascular system ; Cell Movement - drug effects ; Cell Proliferation - drug effects ; Cells, Cultured ; Endothelium, Vascular - drug effects ; Endothelium, Vascular - metabolism ; Essential Hypertension ; Female ; Hyperplasia - drug therapy ; Hyperplasia - metabolism ; Hypertension - drug therapy ; Hypertension - metabolism ; Kv1.3 Potassium Channel - antagonists & inhibitors ; Kv1.3 Potassium Channel - metabolism ; Male ; Medical sciences ; Medicine ; Medicine & Public Health ; Mice ; Muscle, Smooth, Vascular - drug effects ; Muscle, Smooth, Vascular - metabolism ; Original Article ; Pancreatitis-Associated Proteins ; Pharmacology. Drug treatments ; Potassium Channel Blockers - pharmacology ; Tunica Intima - drug effects ; Tunica Intima - metabolism</subject><ispartof>Cardiovascular drugs and therapy, 2014-12, Vol.28 (6), p.501-511</ispartof><rights>Springer Science+Business Media New York 2014</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c487t-e5d70c0d146455fd2f679d80b12eff2a112cff2cbc8f1706e2abd2a4d1ac5e613</citedby><cites>FETCH-LOGICAL-c487t-e5d70c0d146455fd2f679d80b12eff2a112cff2cbc8f1706e2abd2a4d1ac5e613</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10557-014-6554-5$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10557-014-6554-5$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=29054175$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25348824$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cidad, P.</creatorcontrib><creatorcontrib>Novensà, L.</creatorcontrib><creatorcontrib>Garabito, M.</creatorcontrib><creatorcontrib>Batlle, M.</creatorcontrib><creatorcontrib>Dantas, A. P.</creatorcontrib><creatorcontrib>Heras, M.</creatorcontrib><creatorcontrib>López-López, J. R.</creatorcontrib><creatorcontrib>Pérez-García, M. T.</creatorcontrib><creatorcontrib>Roqué, M.</creatorcontrib><title>K+ Channels Expression in Hypertension After Arterial Injury, and Effect of Selective Kv1.3 Blockade with PAP-1 on Intimal Hyperplasia Formation</title><title>Cardiovascular drugs and therapy</title><addtitle>Cardiovasc Drugs Ther</addtitle><addtitle>Cardiovasc Drugs Ther</addtitle><description>Introduction
K
+
channels are central to vascular pathophysiology. Previous results demonstrated that phenotypic modulation associates with a change in Kv1.3 to Kv1.5 expression, and that Kv1.3 blockade inhibits proliferation of VSMCs cultures.
Purpose
To explore whether the Kv1.3 to Kv1.5 switch could be a marker of the increased risk of intimal hyperplasia in essential hypertension and whether systemic treatment with Kv1.3 blockers can prevent intimal hyperplasia after endoluminal lesion .
Methods
Morphometric and immunohistochemical analysis were performed in arterial segments following arterial injury and constant infusion of the Kv1.3 blocker PAP-1 during 28 days. Differential expression of K
+
channel genes was studied in VSMC from hypertensive (BPH) and normotensive (BPN) mice, both in control and after endoluminal lesion. Finally, the migration and proliferation rate of BPN and BPH VSMCs was explored in vitro.
Results
Changes in mRNA expression led to an increased Kv1.3/Kv1.5 ratio in BPH VSMC. Consistent with this, arterial injury in BPH mice induced a higher degree of luminal stenosis, (84 ± 4 % vs. 70 ± 5 % in BPN,
p
< 0.01), although no differences in migration and proliferation rate were observed in cultured VSMCs. The in vivo proliferative lesions were significantly decreased upon PAP-1 systemic infusion (18 ± 6 % vs. 58 ± 20 % with vehicle,
p
< 0.05).
Conclusions
Hypertension leads to a higher degree of luminal stenosis in our arterial injury model, that correlates with a decreased expression of Kv1.5 channels. Kv1.3 blockers decreased in vitro VSMCs proliferation, migration, and in vivo intimal hyperplasia formation, pointing to Kv1.3 channels as promising therapeutical targets against restenosis.</description><subject>Animals</subject><subject>Arterial hypertension. Arterial hypotension</subject><subject>Arteries - drug effects</subject><subject>Arteries - metabolism</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Cardiology</subject><subject>Cardiology. Vascular system</subject><subject>Cardiovascular system</subject><subject>Cell Movement - drug effects</subject><subject>Cell Proliferation - drug effects</subject><subject>Cells, Cultured</subject><subject>Endothelium, Vascular - drug effects</subject><subject>Endothelium, Vascular - metabolism</subject><subject>Essential Hypertension</subject><subject>Female</subject><subject>Hyperplasia - drug therapy</subject><subject>Hyperplasia - metabolism</subject><subject>Hypertension - drug therapy</subject><subject>Hypertension - metabolism</subject><subject>Kv1.3 Potassium Channel - antagonists & inhibitors</subject><subject>Kv1.3 Potassium Channel - metabolism</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mice</subject><subject>Muscle, Smooth, Vascular - drug effects</subject><subject>Muscle, Smooth, Vascular - metabolism</subject><subject>Original Article</subject><subject>Pancreatitis-Associated Proteins</subject><subject>Pharmacology. Drug treatments</subject><subject>Potassium Channel Blockers - pharmacology</subject><subject>Tunica Intima - drug effects</subject><subject>Tunica Intima - metabolism</subject><issn>0920-3206</issn><issn>1573-7241</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc9uEzEQxi0EomnhAbggX5CQiovHa--fY4hSGrUSlYCz5XjHdIPj3dq7hbwFj4zTBLhxGo_8m-_TzEfIK-AXwHn1PgFXqmIcJCuVkkw9ITNQVcEqIeEpmfFGcFYIXp6Q05Q2PM80Tf2cnAhVyLoWckZ-XZ_TxZ0JAX2iy59DxJS6PtAu0KvdgHHE8NjP3YiRznMfO-PpKmymuHtHTWjp0jm0I-0d_Yw-v7oHpNcPcFHQD763302L9Ec33tHb-S0DmrVWYey2WeTRYPAmdYZe9nFrxuz0gjxzxid8eaxn5Ovl8sviit18-rhazG-YlXU1MlRtxS1vQZZSKdcKV1ZNW_M1CHROGABhc7VrWzuoeInCrFthZAvGKiyhOCNvD7pD7O8nTKPedsmi9yZgPyUNZaE4r1UpMgoH1MY-pYhODzEvEHcauN4HoQ9B6ByE3gehVZ55fZSf1lts_078uXwG3hwBk6zxLppgu_SPa7iSUO2FxIFL-St8w6g3_RRDPs1_3H8D9Omg5A</recordid><startdate>20141201</startdate><enddate>20141201</enddate><creator>Cidad, P.</creator><creator>Novensà, L.</creator><creator>Garabito, M.</creator><creator>Batlle, M.</creator><creator>Dantas, A. P.</creator><creator>Heras, M.</creator><creator>López-López, J. R.</creator><creator>Pérez-García, M. T.</creator><creator>Roqué, M.</creator><general>Springer US</general><general>Springer</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>20141201</creationdate><title>K+ Channels Expression in Hypertension After Arterial Injury, and Effect of Selective Kv1.3 Blockade with PAP-1 on Intimal Hyperplasia Formation</title><author>Cidad, P. ; Novensà, L. ; Garabito, M. ; Batlle, M. ; Dantas, A. P. ; Heras, M. ; López-López, J. R. ; Pérez-García, M. T. ; Roqué, M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c487t-e5d70c0d146455fd2f679d80b12eff2a112cff2cbc8f1706e2abd2a4d1ac5e613</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>Arterial hypertension. Arterial hypotension</topic><topic>Arteries - drug effects</topic><topic>Arteries - metabolism</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Cardiology</topic><topic>Cardiology. Vascular system</topic><topic>Cardiovascular system</topic><topic>Cell Movement - drug effects</topic><topic>Cell Proliferation - drug effects</topic><topic>Cells, Cultured</topic><topic>Endothelium, Vascular - drug effects</topic><topic>Endothelium, Vascular - metabolism</topic><topic>Essential Hypertension</topic><topic>Female</topic><topic>Hyperplasia - drug therapy</topic><topic>Hyperplasia - metabolism</topic><topic>Hypertension - drug therapy</topic><topic>Hypertension - metabolism</topic><topic>Kv1.3 Potassium Channel - antagonists & inhibitors</topic><topic>Kv1.3 Potassium Channel - metabolism</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mice</topic><topic>Muscle, Smooth, Vascular - drug effects</topic><topic>Muscle, Smooth, Vascular - metabolism</topic><topic>Original Article</topic><topic>Pancreatitis-Associated Proteins</topic><topic>Pharmacology. Drug treatments</topic><topic>Potassium Channel Blockers - pharmacology</topic><topic>Tunica Intima - drug effects</topic><topic>Tunica Intima - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cidad, P.</creatorcontrib><creatorcontrib>Novensà, L.</creatorcontrib><creatorcontrib>Garabito, M.</creatorcontrib><creatorcontrib>Batlle, M.</creatorcontrib><creatorcontrib>Dantas, A. P.</creatorcontrib><creatorcontrib>Heras, M.</creatorcontrib><creatorcontrib>López-López, J. R.</creatorcontrib><creatorcontrib>Pérez-García, M. T.</creatorcontrib><creatorcontrib>Roqué, 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>MEDLINE - Academic</collection><jtitle>Cardiovascular drugs and therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cidad, P.</au><au>Novensà, L.</au><au>Garabito, M.</au><au>Batlle, M.</au><au>Dantas, A. P.</au><au>Heras, M.</au><au>López-López, J. R.</au><au>Pérez-García, M. T.</au><au>Roqué, M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>K+ Channels Expression in Hypertension After Arterial Injury, and Effect of Selective Kv1.3 Blockade with PAP-1 on Intimal Hyperplasia Formation</atitle><jtitle>Cardiovascular drugs and therapy</jtitle><stitle>Cardiovasc Drugs Ther</stitle><addtitle>Cardiovasc Drugs Ther</addtitle><date>2014-12-01</date><risdate>2014</risdate><volume>28</volume><issue>6</issue><spage>501</spage><epage>511</epage><pages>501-511</pages><issn>0920-3206</issn><eissn>1573-7241</eissn><coden>CDTHET</coden><abstract>Introduction
K
+
channels are central to vascular pathophysiology. Previous results demonstrated that phenotypic modulation associates with a change in Kv1.3 to Kv1.5 expression, and that Kv1.3 blockade inhibits proliferation of VSMCs cultures.
Purpose
To explore whether the Kv1.3 to Kv1.5 switch could be a marker of the increased risk of intimal hyperplasia in essential hypertension and whether systemic treatment with Kv1.3 blockers can prevent intimal hyperplasia after endoluminal lesion .
Methods
Morphometric and immunohistochemical analysis were performed in arterial segments following arterial injury and constant infusion of the Kv1.3 blocker PAP-1 during 28 days. Differential expression of K
+
channel genes was studied in VSMC from hypertensive (BPH) and normotensive (BPN) mice, both in control and after endoluminal lesion. Finally, the migration and proliferation rate of BPN and BPH VSMCs was explored in vitro.
Results
Changes in mRNA expression led to an increased Kv1.3/Kv1.5 ratio in BPH VSMC. Consistent with this, arterial injury in BPH mice induced a higher degree of luminal stenosis, (84 ± 4 % vs. 70 ± 5 % in BPN,
p
< 0.01), although no differences in migration and proliferation rate were observed in cultured VSMCs. The in vivo proliferative lesions were significantly decreased upon PAP-1 systemic infusion (18 ± 6 % vs. 58 ± 20 % with vehicle,
p
< 0.05).
Conclusions
Hypertension leads to a higher degree of luminal stenosis in our arterial injury model, that correlates with a decreased expression of Kv1.5 channels. Kv1.3 blockers decreased in vitro VSMCs proliferation, migration, and in vivo intimal hyperplasia formation, pointing to Kv1.3 channels as promising therapeutical targets against restenosis.</abstract><cop>Boston</cop><pub>Springer US</pub><pmid>25348824</pmid><doi>10.1007/s10557-014-6554-5</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
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| ispartof | Cardiovascular drugs and therapy, 2014-12, Vol.28 (6), p.501-511 |
| issn | 0920-3206 1573-7241 |
| language | eng |
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| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Animals Arterial hypertension. Arterial hypotension Arteries - drug effects Arteries - metabolism Biological and medical sciences Blood and lymphatic vessels Cardiology Cardiology. Vascular system Cardiovascular system Cell Movement - drug effects Cell Proliferation - drug effects Cells, Cultured Endothelium, Vascular - drug effects Endothelium, Vascular - metabolism Essential Hypertension Female Hyperplasia - drug therapy Hyperplasia - metabolism Hypertension - drug therapy Hypertension - metabolism Kv1.3 Potassium Channel - antagonists & inhibitors Kv1.3 Potassium Channel - metabolism Male Medical sciences Medicine Medicine & Public Health Mice Muscle, Smooth, Vascular - drug effects Muscle, Smooth, Vascular - metabolism Original Article Pancreatitis-Associated Proteins Pharmacology. Drug treatments Potassium Channel Blockers - pharmacology Tunica Intima - drug effects Tunica Intima - metabolism |
| title | K+ Channels Expression in Hypertension After Arterial Injury, and Effect of Selective Kv1.3 Blockade with PAP-1 on Intimal Hyperplasia Formation |
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