8-Chloro-cAMP inhibits smooth muscle cell proliferation in vitro and neointima formation induced by balloon injury in vivo
OBJECTIVES The aims of the present study were to assess 1) the effect of 8-Cl-cAMP (cyclic-3′-5′-adenosine monophosphate) on vascular smooth muscle cell (VSMC) proliferation in vitro and 2) the efficacy of systemic administration of 8-Cl-cAMP on neointimal formation after balloon injury in vivo. BAC...
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| Veröffentlicht in: | Journal of the American College of Cardiology 2000-07, Vol.36 (1), p.288-293 |
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| creator | Indolfi, Ciro Di Lorenzo, Emilio Rapacciuolo, Antonio Stingone, Angela Maria Stabile, Eugenio Leccia, Antonio Torella, Daniele Caputo, Rosa Ciardiello, Fortunato Tortora, Gianpaolo Chiariello, Massimo |
| description | OBJECTIVES
The aims of the present study were to assess 1) the effect of 8-Cl-cAMP (cyclic-3′-5′-adenosine monophosphate) on vascular smooth muscle cell (VSMC) proliferation in vitro and 2) the efficacy of systemic administration of 8-Cl-cAMP on neointimal formation after balloon injury in vivo.
BACKGROUND
Neointimal formation after vascular injury is responsible for restenosis after arterial stenting. Recently, 8-Cl-cAMP, a cAMP analogue that induces growth arrest, has been safely administered in phase I studies in humans.
METHODS
The effect of 8-Cl-cAMP on cell proliferation was first assessed on SMCs in vitro. To study the effects of cAMP in vivo, balloon injury was performed in 67 rats using a 2F Fogarty balloon catheter.
RESULTS
The 8-Cl-cAMP markedly inhibited VSMC proliferation in vitro, reduced protein kinase A (PKA) RIα subunit expression, and induced PKA RIIβ subunit expression. In addition, 8-Cl-cAMP reduced, in a dose-dependent manner, neointimal area and neointima/media ratio after balloon injury. The proliferative activity, assessed by proliferating nuclear cell antigen immunostaining, revealed a reduction of proliferative activity of VSMCs in vivo in the 8-Cl-cAMP group. Moreover, the systemic administration of 8-Cl-cAMP did not affect renal function, blood pressure and heart rate.
CONCLUSIONS
We conclude that 8-Cl-cAMP potently inhibits VSMC proliferation in vitro and reduces neointima formation by balloon injury in vivo after systemic administration. These data may have a clinical relevance in designing future strategies to prevent restenosis after arterial stenting and perhaps after percutaneous transluminal coronary angioplasty. |
| doi_str_mv | 10.1016/S0735-1097(00)00679-3 |
| format | Article |
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The aims of the present study were to assess 1) the effect of 8-Cl-cAMP (cyclic-3′-5′-adenosine monophosphate) on vascular smooth muscle cell (VSMC) proliferation in vitro and 2) the efficacy of systemic administration of 8-Cl-cAMP on neointimal formation after balloon injury in vivo.
BACKGROUND
Neointimal formation after vascular injury is responsible for restenosis after arterial stenting. Recently, 8-Cl-cAMP, a cAMP analogue that induces growth arrest, has been safely administered in phase I studies in humans.
METHODS
The effect of 8-Cl-cAMP on cell proliferation was first assessed on SMCs in vitro. To study the effects of cAMP in vivo, balloon injury was performed in 67 rats using a 2F Fogarty balloon catheter.
RESULTS
The 8-Cl-cAMP markedly inhibited VSMC proliferation in vitro, reduced protein kinase A (PKA) RIα subunit expression, and induced PKA RIIβ subunit expression. In addition, 8-Cl-cAMP reduced, in a dose-dependent manner, neointimal area and neointima/media ratio after balloon injury. The proliferative activity, assessed by proliferating nuclear cell antigen immunostaining, revealed a reduction of proliferative activity of VSMCs in vivo in the 8-Cl-cAMP group. Moreover, the systemic administration of 8-Cl-cAMP did not affect renal function, blood pressure and heart rate.
CONCLUSIONS
We conclude that 8-Cl-cAMP potently inhibits VSMC proliferation in vitro and reduces neointima formation by balloon injury in vivo after systemic administration. These data may have a clinical relevance in designing future strategies to prevent restenosis after arterial stenting and perhaps after percutaneous transluminal coronary angioplasty.</description><identifier>ISSN: 0735-1097</identifier><identifier>EISSN: 1558-3597</identifier><identifier>DOI: 10.1016/S0735-1097(00)00679-3</identifier><identifier>PMID: 10898448</identifier><identifier>CODEN: JACCDI</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>8-Bromo Cyclic Adenosine Monophosphate - administration & dosage ; 8-Bromo Cyclic Adenosine Monophosphate - analogs & derivatives ; 8-Bromo Cyclic Adenosine Monophosphate - pharmacology ; Animals ; Antineoplastic Agents - administration & dosage ; Antineoplastic Agents - pharmacology ; Aorta, Thoracic - injuries ; Aorta, Thoracic - pathology ; Arterial Occlusive Diseases - enzymology ; Arterial Occlusive Diseases - metabolism ; Arterial Occlusive Diseases - prevention & control ; Biological and medical sciences ; Blood Pressure - drug effects ; Catheterization - adverse effects ; Cell Division - drug effects ; Cells, Cultured ; Cyclic AMP-Dependent Protein Kinase RIalpha Subunit ; Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit ; Cyclic AMP-Dependent Protein Kinases - metabolism ; Diseases of the cardiovascular system ; Down-Regulation - drug effects ; Heart Rate - drug effects ; Injections, Intraperitoneal ; Medical sciences ; Muscle, Smooth, Vascular - cytology ; Muscle, Smooth, Vascular - drug effects ; Muscle, Smooth, Vascular - enzymology ; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects) ; Rats ; Rats, Wistar ; Tunica Intima - cytology ; Tunica Intima - drug effects ; Tunica Intima - enzymology ; Up-Regulation - drug effects</subject><ispartof>Journal of the American College of Cardiology, 2000-07, Vol.36 (1), p.288-293</ispartof><rights>2000 American College of Cardiology</rights><rights>2000 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c492t-1e5e7b51e8d9a61bfbe8741e4e719261dddfdd0aad1bfe499cc5c27e5dd833cb3</citedby><cites>FETCH-LOGICAL-c492t-1e5e7b51e8d9a61bfbe8741e4e719261dddfdd0aad1bfe499cc5c27e5dd833cb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0735-1097(00)00679-3$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>315,782,786,3552,27931,27932,46002</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1410163$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10898448$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Indolfi, Ciro</creatorcontrib><creatorcontrib>Di Lorenzo, Emilio</creatorcontrib><creatorcontrib>Rapacciuolo, Antonio</creatorcontrib><creatorcontrib>Stingone, Angela Maria</creatorcontrib><creatorcontrib>Stabile, Eugenio</creatorcontrib><creatorcontrib>Leccia, Antonio</creatorcontrib><creatorcontrib>Torella, Daniele</creatorcontrib><creatorcontrib>Caputo, Rosa</creatorcontrib><creatorcontrib>Ciardiello, Fortunato</creatorcontrib><creatorcontrib>Tortora, Gianpaolo</creatorcontrib><creatorcontrib>Chiariello, Massimo</creatorcontrib><title>8-Chloro-cAMP inhibits smooth muscle cell proliferation in vitro and neointima formation induced by balloon injury in vivo</title><title>Journal of the American College of Cardiology</title><addtitle>J Am Coll Cardiol</addtitle><description>OBJECTIVES
The aims of the present study were to assess 1) the effect of 8-Cl-cAMP (cyclic-3′-5′-adenosine monophosphate) on vascular smooth muscle cell (VSMC) proliferation in vitro and 2) the efficacy of systemic administration of 8-Cl-cAMP on neointimal formation after balloon injury in vivo.
BACKGROUND
Neointimal formation after vascular injury is responsible for restenosis after arterial stenting. Recently, 8-Cl-cAMP, a cAMP analogue that induces growth arrest, has been safely administered in phase I studies in humans.
METHODS
The effect of 8-Cl-cAMP on cell proliferation was first assessed on SMCs in vitro. To study the effects of cAMP in vivo, balloon injury was performed in 67 rats using a 2F Fogarty balloon catheter.
RESULTS
The 8-Cl-cAMP markedly inhibited VSMC proliferation in vitro, reduced protein kinase A (PKA) RIα subunit expression, and induced PKA RIIβ subunit expression. In addition, 8-Cl-cAMP reduced, in a dose-dependent manner, neointimal area and neointima/media ratio after balloon injury. The proliferative activity, assessed by proliferating nuclear cell antigen immunostaining, revealed a reduction of proliferative activity of VSMCs in vivo in the 8-Cl-cAMP group. Moreover, the systemic administration of 8-Cl-cAMP did not affect renal function, blood pressure and heart rate.
CONCLUSIONS
We conclude that 8-Cl-cAMP potently inhibits VSMC proliferation in vitro and reduces neointima formation by balloon injury in vivo after systemic administration. These data may have a clinical relevance in designing future strategies to prevent restenosis after arterial stenting and perhaps after percutaneous transluminal coronary angioplasty.</description><subject>8-Bromo Cyclic Adenosine Monophosphate - administration & dosage</subject><subject>8-Bromo Cyclic Adenosine Monophosphate - analogs & derivatives</subject><subject>8-Bromo Cyclic Adenosine Monophosphate - pharmacology</subject><subject>Animals</subject><subject>Antineoplastic Agents - administration & dosage</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Aorta, Thoracic - injuries</subject><subject>Aorta, Thoracic - pathology</subject><subject>Arterial Occlusive Diseases - enzymology</subject><subject>Arterial Occlusive Diseases - metabolism</subject><subject>Arterial Occlusive Diseases - prevention & control</subject><subject>Biological and medical sciences</subject><subject>Blood Pressure - drug effects</subject><subject>Catheterization - adverse effects</subject><subject>Cell Division - drug effects</subject><subject>Cells, Cultured</subject><subject>Cyclic AMP-Dependent Protein Kinase RIalpha Subunit</subject><subject>Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit</subject><subject>Cyclic AMP-Dependent Protein Kinases - metabolism</subject><subject>Diseases of the cardiovascular system</subject><subject>Down-Regulation - drug effects</subject><subject>Heart Rate - drug effects</subject><subject>Injections, Intraperitoneal</subject><subject>Medical sciences</subject><subject>Muscle, Smooth, Vascular - cytology</subject><subject>Muscle, Smooth, Vascular - drug effects</subject><subject>Muscle, Smooth, Vascular - enzymology</subject><subject>Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects)</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Tunica Intima - cytology</subject><subject>Tunica Intima - drug effects</subject><subject>Tunica Intima - enzymology</subject><subject>Up-Regulation - drug effects</subject><issn>0735-1097</issn><issn>1558-3597</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkF1vFCEUhomxsdvqT7Dhwph6MQrLsMBVs9m0atJGE_WaMHAmS8MMLcxssv76Mjvrx12vSOB5D-d9EHpLyUdK6OrTDyIYryhR4pKQD4SshKrYC7SgnMuKcSVeosVf5BSd5XxPCiWpeoVOKZFK1rVcoN-y2mxDTLGy67vv2Pdb3_gh49zFOGxxN2YbAFsIAT-kGHwLyQw-9oXEOz-kiE3vcA_R94PvDG5j6v4AbrTgcLPHjQkhHq7ux7Sfo7v4Gp20JmR4czzP0a-b65-bL9Xtt89fN-vbytZqOVQUOIiGU5BOmRVt2gakqCnUIKharqhzrnWOGOPKG9RKWcvtUgB3TjJmG3aO3s9zS4HHEfKgO5-nRqasPWYt6JLVjMsC8hm0KeacoNUPqXRKe02JnqTrg3Q9GdWE6IN0zUru4vjB2HTg_kvNlgvw7giYbE1ok-mtz_-4eho-zbmaMSg2dh6SztZDXyT6BHbQLvpnNnkCuKihLA</recordid><startdate>20000701</startdate><enddate>20000701</enddate><creator>Indolfi, Ciro</creator><creator>Di Lorenzo, Emilio</creator><creator>Rapacciuolo, Antonio</creator><creator>Stingone, Angela Maria</creator><creator>Stabile, Eugenio</creator><creator>Leccia, Antonio</creator><creator>Torella, Daniele</creator><creator>Caputo, Rosa</creator><creator>Ciardiello, Fortunato</creator><creator>Tortora, Gianpaolo</creator><creator>Chiariello, Massimo</creator><general>Elsevier Inc</general><general>Elsevier Science</general><scope>6I.</scope><scope>AAFTH</scope><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>20000701</creationdate><title>8-Chloro-cAMP inhibits smooth muscle cell proliferation in vitro and neointima formation induced by balloon injury in vivo</title><author>Indolfi, Ciro ; Di Lorenzo, Emilio ; Rapacciuolo, Antonio ; Stingone, Angela Maria ; Stabile, Eugenio ; Leccia, Antonio ; Torella, Daniele ; Caputo, Rosa ; Ciardiello, Fortunato ; Tortora, Gianpaolo ; Chiariello, Massimo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c492t-1e5e7b51e8d9a61bfbe8741e4e719261dddfdd0aad1bfe499cc5c27e5dd833cb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>8-Bromo Cyclic Adenosine Monophosphate - administration & dosage</topic><topic>8-Bromo Cyclic Adenosine Monophosphate - analogs & derivatives</topic><topic>8-Bromo Cyclic Adenosine Monophosphate - pharmacology</topic><topic>Animals</topic><topic>Antineoplastic Agents - administration & dosage</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Aorta, Thoracic - injuries</topic><topic>Aorta, Thoracic - pathology</topic><topic>Arterial Occlusive Diseases - enzymology</topic><topic>Arterial Occlusive Diseases - metabolism</topic><topic>Arterial Occlusive Diseases - prevention & control</topic><topic>Biological and medical sciences</topic><topic>Blood Pressure - drug effects</topic><topic>Catheterization - adverse effects</topic><topic>Cell Division - drug effects</topic><topic>Cells, Cultured</topic><topic>Cyclic AMP-Dependent Protein Kinase RIalpha Subunit</topic><topic>Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit</topic><topic>Cyclic AMP-Dependent Protein Kinases - metabolism</topic><topic>Diseases of the cardiovascular system</topic><topic>Down-Regulation - drug effects</topic><topic>Heart Rate - drug effects</topic><topic>Injections, Intraperitoneal</topic><topic>Medical sciences</topic><topic>Muscle, Smooth, Vascular - cytology</topic><topic>Muscle, Smooth, Vascular - drug effects</topic><topic>Muscle, Smooth, Vascular - enzymology</topic><topic>Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects)</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Tunica Intima - cytology</topic><topic>Tunica Intima - drug effects</topic><topic>Tunica Intima - enzymology</topic><topic>Up-Regulation - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Indolfi, Ciro</creatorcontrib><creatorcontrib>Di Lorenzo, Emilio</creatorcontrib><creatorcontrib>Rapacciuolo, Antonio</creatorcontrib><creatorcontrib>Stingone, Angela Maria</creatorcontrib><creatorcontrib>Stabile, Eugenio</creatorcontrib><creatorcontrib>Leccia, Antonio</creatorcontrib><creatorcontrib>Torella, Daniele</creatorcontrib><creatorcontrib>Caputo, Rosa</creatorcontrib><creatorcontrib>Ciardiello, Fortunato</creatorcontrib><creatorcontrib>Tortora, Gianpaolo</creatorcontrib><creatorcontrib>Chiariello, Massimo</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><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>Journal of the American College of Cardiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Indolfi, Ciro</au><au>Di Lorenzo, Emilio</au><au>Rapacciuolo, Antonio</au><au>Stingone, Angela Maria</au><au>Stabile, Eugenio</au><au>Leccia, Antonio</au><au>Torella, Daniele</au><au>Caputo, Rosa</au><au>Ciardiello, Fortunato</au><au>Tortora, Gianpaolo</au><au>Chiariello, Massimo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>8-Chloro-cAMP inhibits smooth muscle cell proliferation in vitro and neointima formation induced by balloon injury in vivo</atitle><jtitle>Journal of the American College of Cardiology</jtitle><addtitle>J Am Coll Cardiol</addtitle><date>2000-07-01</date><risdate>2000</risdate><volume>36</volume><issue>1</issue><spage>288</spage><epage>293</epage><pages>288-293</pages><issn>0735-1097</issn><eissn>1558-3597</eissn><coden>JACCDI</coden><abstract>OBJECTIVES
The aims of the present study were to assess 1) the effect of 8-Cl-cAMP (cyclic-3′-5′-adenosine monophosphate) on vascular smooth muscle cell (VSMC) proliferation in vitro and 2) the efficacy of systemic administration of 8-Cl-cAMP on neointimal formation after balloon injury in vivo.
BACKGROUND
Neointimal formation after vascular injury is responsible for restenosis after arterial stenting. Recently, 8-Cl-cAMP, a cAMP analogue that induces growth arrest, has been safely administered in phase I studies in humans.
METHODS
The effect of 8-Cl-cAMP on cell proliferation was first assessed on SMCs in vitro. To study the effects of cAMP in vivo, balloon injury was performed in 67 rats using a 2F Fogarty balloon catheter.
RESULTS
The 8-Cl-cAMP markedly inhibited VSMC proliferation in vitro, reduced protein kinase A (PKA) RIα subunit expression, and induced PKA RIIβ subunit expression. In addition, 8-Cl-cAMP reduced, in a dose-dependent manner, neointimal area and neointima/media ratio after balloon injury. The proliferative activity, assessed by proliferating nuclear cell antigen immunostaining, revealed a reduction of proliferative activity of VSMCs in vivo in the 8-Cl-cAMP group. Moreover, the systemic administration of 8-Cl-cAMP did not affect renal function, blood pressure and heart rate.
CONCLUSIONS
We conclude that 8-Cl-cAMP potently inhibits VSMC proliferation in vitro and reduces neointima formation by balloon injury in vivo after systemic administration. These data may have a clinical relevance in designing future strategies to prevent restenosis after arterial stenting and perhaps after percutaneous transluminal coronary angioplasty.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>10898448</pmid><doi>10.1016/S0735-1097(00)00679-3</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0735-1097 |
| ispartof | Journal of the American College of Cardiology, 2000-07, Vol.36 (1), p.288-293 |
| issn | 0735-1097 1558-3597 |
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| subjects | 8-Bromo Cyclic Adenosine Monophosphate - administration & dosage 8-Bromo Cyclic Adenosine Monophosphate - analogs & derivatives 8-Bromo Cyclic Adenosine Monophosphate - pharmacology Animals Antineoplastic Agents - administration & dosage Antineoplastic Agents - pharmacology Aorta, Thoracic - injuries Aorta, Thoracic - pathology Arterial Occlusive Diseases - enzymology Arterial Occlusive Diseases - metabolism Arterial Occlusive Diseases - prevention & control Biological and medical sciences Blood Pressure - drug effects Catheterization - adverse effects Cell Division - drug effects Cells, Cultured Cyclic AMP-Dependent Protein Kinase RIalpha Subunit Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit Cyclic AMP-Dependent Protein Kinases - metabolism Diseases of the cardiovascular system Down-Regulation - drug effects Heart Rate - drug effects Injections, Intraperitoneal Medical sciences Muscle, Smooth, Vascular - cytology Muscle, Smooth, Vascular - drug effects Muscle, Smooth, Vascular - enzymology Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects) Rats Rats, Wistar Tunica Intima - cytology Tunica Intima - drug effects Tunica Intima - enzymology Up-Regulation - drug effects |
| title | 8-Chloro-cAMP inhibits smooth muscle cell proliferation in vitro and neointima formation induced by balloon injury in vivo |
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