Inhibition of In-Stent Stenosis by Oral Administration of Bindarit in Porcine Coronary Arteries
OBJECTIVE—We have previously demonstrated that bindarit, a selective inhibitor of monocyte chemotactic proteins (MCPs), is effective in reducing neointimal formation in rodent models of vascular injury by reducing smooth muscle cell proliferation and migration and neointimal macrophage content, effe...
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| Veröffentlicht in: | Arteriosclerosis, thrombosis, and vascular biology thrombosis, and vascular biology, 2011-11, Vol.31 (11), p.2448-2454 |
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| creator | Ialenti, Armando Grassia, Gianluca Gordon, Peter Maddaluno, Marcella Di Lauro, Maria Vittoria Baker, Andrew H Guglielmotti, Angelo Colombo, Antonio Biondi, Giuseppe Kennedy, Simon Maffia, Pasquale |
| description | OBJECTIVE—We have previously demonstrated that bindarit, a selective inhibitor of monocyte chemotactic proteins (MCPs), is effective in reducing neointimal formation in rodent models of vascular injury by reducing smooth muscle cell proliferation and migration and neointimal macrophage content, effects associated with the inhibition of MCP-1/CCL2 production. The aim of the current study was to evaluate the efficacy of bindarit on in-stent stenosis in the preclinical porcine coronary stent model.
METHODS AND RESULTS—One or 2 bare metal stents (Multi-Link Vision, 3.5 mm) were deployed (1:1.2 oversize ratio) in the coronary arteries of 42 pigs (20 bindarit versus 22 controls). Bindarit (50 mg/kg per day) was administered orally from 2 days before stenting until the time of euthanasia at 7 and 28 days. Bindarit caused a significant reduction in neointimal area (39.4%, P |
| doi_str_mv | 10.1161/ATVBAHA.111.230078 |
| format | Article |
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METHODS AND RESULTS—One or 2 bare metal stents (Multi-Link Vision, 3.5 mm) were deployed (1:1.2 oversize ratio) in the coronary arteries of 42 pigs (20 bindarit versus 22 controls). Bindarit (50 mg/kg per day) was administered orally from 2 days before stenting until the time of euthanasia at 7 and 28 days. Bindarit caused a significant reduction in neointimal area (39.4%, P<0.001, n=9 group), neointimal thickness (51%, P<0.001), stenosis area (37%, P<0.001), and inflammatory score (40%, P<0.001) compared with control animals, whereas there was no significant difference in the injury score between the 2 groups. Moreover, treatment with bindarit significantly reduced the number of proliferating cells (by 45%, P<0.05; n=6 group) and monocyte/macrophage content (by 55%, P<0.01; n=5–6 group) in stented arteries at day 7 and 28, respectively. These effects were associated with a significant (P<0.05) reduction of MCP-1 plasma levels at day 28. In vitro data showed that bindarit (10–300 μmol/L) reduced tumor necrosis factor-α (50 ng/mL)–induced pig coronary artery smooth muscle cell proliferation and inhibited MCP-1 production.
CONCLUSION—Our results show the efficacy of bindarit in the prevention of porcine in-stent stenosis and support further investigation for clinical application of this compound.]]></description><identifier>ISSN: 1079-5642</identifier><identifier>EISSN: 1524-4636</identifier><identifier>DOI: 10.1161/ATVBAHA.111.230078</identifier><identifier>PMID: 21852559</identifier><identifier>CODEN: ATVBFA</identifier><language>eng</language><publisher>Philadelphia, PA: American Heart Association, Inc</publisher><subject>Administration, Oral ; Animals ; Atherosclerosis (general aspects, experimental research) ; Biological and medical sciences ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Cell Proliferation - drug effects ; Coronary heart disease ; Coronary Stenosis - pathology ; Coronary Stenosis - prevention & control ; Coronary Vessels - drug effects ; Coronary Vessels - pathology ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; Heart ; Indazoles - administration & dosage ; Indazoles - pharmacology ; Indazoles - therapeutic use ; Male ; Medical sciences ; Models, Animal ; Monocyte Chemoattractant Proteins - antagonists & inhibitors ; Monocyte Chemoattractant Proteins - blood ; Muscle, Smooth, Vascular - drug effects ; Muscle, Smooth, Vascular - pathology ; Neointima - pathology ; Neointima - prevention & control ; Propionates - administration & dosage ; Propionates - pharmacology ; Propionates - therapeutic use ; Stents ; Swine ; Treatment Outcome</subject><ispartof>Arteriosclerosis, thrombosis, and vascular biology, 2011-11, Vol.31 (11), p.2448-2454</ispartof><rights>2011 American Heart Association, Inc.</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5388-7a303aedfc95b29d5274616758ee663d259fea0d30a1a0c750a1686191d6743</citedby><cites>FETCH-LOGICAL-c5388-7a303aedfc95b29d5274616758ee663d259fea0d30a1a0c750a1686191d6743</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25285969$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21852559$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ialenti, Armando</creatorcontrib><creatorcontrib>Grassia, Gianluca</creatorcontrib><creatorcontrib>Gordon, Peter</creatorcontrib><creatorcontrib>Maddaluno, Marcella</creatorcontrib><creatorcontrib>Di Lauro, Maria Vittoria</creatorcontrib><creatorcontrib>Baker, Andrew H</creatorcontrib><creatorcontrib>Guglielmotti, Angelo</creatorcontrib><creatorcontrib>Colombo, Antonio</creatorcontrib><creatorcontrib>Biondi, Giuseppe</creatorcontrib><creatorcontrib>Kennedy, Simon</creatorcontrib><creatorcontrib>Maffia, Pasquale</creatorcontrib><title>Inhibition of In-Stent Stenosis by Oral Administration of Bindarit in Porcine Coronary Arteries</title><title>Arteriosclerosis, thrombosis, and vascular biology</title><addtitle>Arterioscler Thromb Vasc Biol</addtitle><description><![CDATA[OBJECTIVE—We have previously demonstrated that bindarit, a selective inhibitor of monocyte chemotactic proteins (MCPs), is effective in reducing neointimal formation in rodent models of vascular injury by reducing smooth muscle cell proliferation and migration and neointimal macrophage content, effects associated with the inhibition of MCP-1/CCL2 production. The aim of the current study was to evaluate the efficacy of bindarit on in-stent stenosis in the preclinical porcine coronary stent model.
METHODS AND RESULTS—One or 2 bare metal stents (Multi-Link Vision, 3.5 mm) were deployed (1:1.2 oversize ratio) in the coronary arteries of 42 pigs (20 bindarit versus 22 controls). Bindarit (50 mg/kg per day) was administered orally from 2 days before stenting until the time of euthanasia at 7 and 28 days. Bindarit caused a significant reduction in neointimal area (39.4%, P<0.001, n=9 group), neointimal thickness (51%, P<0.001), stenosis area (37%, P<0.001), and inflammatory score (40%, P<0.001) compared with control animals, whereas there was no significant difference in the injury score between the 2 groups. Moreover, treatment with bindarit significantly reduced the number of proliferating cells (by 45%, P<0.05; n=6 group) and monocyte/macrophage content (by 55%, P<0.01; n=5–6 group) in stented arteries at day 7 and 28, respectively. These effects were associated with a significant (P<0.05) reduction of MCP-1 plasma levels at day 28. In vitro data showed that bindarit (10–300 μmol/L) reduced tumor necrosis factor-α (50 ng/mL)–induced pig coronary artery smooth muscle cell proliferation and inhibited MCP-1 production.
CONCLUSION—Our results show the efficacy of bindarit in the prevention of porcine in-stent stenosis and support further investigation for clinical application of this compound.]]></description><subject>Administration, Oral</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>Cell Proliferation - drug effects</subject><subject>Coronary heart disease</subject><subject>Coronary Stenosis - pathology</subject><subject>Coronary Stenosis - prevention & control</subject><subject>Coronary Vessels - drug effects</subject><subject>Coronary Vessels - pathology</subject><subject>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</subject><subject>Heart</subject><subject>Indazoles - administration & dosage</subject><subject>Indazoles - pharmacology</subject><subject>Indazoles - therapeutic use</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Models, Animal</subject><subject>Monocyte Chemoattractant Proteins - antagonists & inhibitors</subject><subject>Monocyte Chemoattractant Proteins - blood</subject><subject>Muscle, Smooth, Vascular - drug effects</subject><subject>Muscle, Smooth, Vascular - pathology</subject><subject>Neointima - pathology</subject><subject>Neointima - prevention & control</subject><subject>Propionates - administration & dosage</subject><subject>Propionates - pharmacology</subject><subject>Propionates - therapeutic use</subject><subject>Stents</subject><subject>Swine</subject><subject>Treatment Outcome</subject><issn>1079-5642</issn><issn>1524-4636</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM9LwzAUx4Mobk7_AQ-Si3jqzI8mbY_dUDcYTNjwGrI2ZdE2mUnH2H9vRju9eXnvfeHzHo8PAPcYjTHm-Dlff0zyWR4CHhOKUJJegCFmJI5iTvllmFGSRYzHZABuvP9ECMWEoGswIDhlhLFsCMTcbPVGt9oaaCs4N9GqVaaFp2q99nBzhEsna5iXjTbat06e2Yk2pXS6hdrAd-sKbRScWmeNdEeYu1Y5rfwtuKpk7dVd30dg9fqyns6ixfJtPs0XUcFomkaJpIhKVVZFxjYkKxlJYo55wlKlOKclYVmlJCopkliiImGh85TjDJc8iekIPHVXd85-75VvRaN9oepaGmX3XmSIY0ZxSgNJOrJw1nunKrFzugkfC4zEyarorYaARWc1LD305_ebRpW_K2eNAXjsAekLWVdOmkL7P46RlGX8xPGOO9g6-PFf9f6gnNgqWbfb_z74AUBhkKI</recordid><startdate>201111</startdate><enddate>201111</enddate><creator>Ialenti, Armando</creator><creator>Grassia, Gianluca</creator><creator>Gordon, Peter</creator><creator>Maddaluno, Marcella</creator><creator>Di Lauro, Maria Vittoria</creator><creator>Baker, Andrew H</creator><creator>Guglielmotti, Angelo</creator><creator>Colombo, Antonio</creator><creator>Biondi, Giuseppe</creator><creator>Kennedy, Simon</creator><creator>Maffia, Pasquale</creator><general>American Heart Association, Inc</general><general>Lippincott Williams & Wilkins</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>201111</creationdate><title>Inhibition of In-Stent Stenosis by Oral Administration of Bindarit in Porcine Coronary Arteries</title><author>Ialenti, Armando ; Grassia, Gianluca ; Gordon, Peter ; Maddaluno, Marcella ; Di Lauro, Maria Vittoria ; Baker, Andrew H ; Guglielmotti, Angelo ; Colombo, Antonio ; Biondi, Giuseppe ; Kennedy, Simon ; Maffia, Pasquale</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5388-7a303aedfc95b29d5274616758ee663d259fea0d30a1a0c750a1686191d6743</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Administration, Oral</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>Cell Proliferation - drug effects</topic><topic>Coronary heart disease</topic><topic>Coronary Stenosis - pathology</topic><topic>Coronary Stenosis - prevention & control</topic><topic>Coronary Vessels - drug effects</topic><topic>Coronary Vessels - pathology</topic><topic>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</topic><topic>Heart</topic><topic>Indazoles - administration & dosage</topic><topic>Indazoles - pharmacology</topic><topic>Indazoles - therapeutic use</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Models, Animal</topic><topic>Monocyte Chemoattractant Proteins - antagonists & inhibitors</topic><topic>Monocyte Chemoattractant Proteins - blood</topic><topic>Muscle, Smooth, Vascular - drug effects</topic><topic>Muscle, Smooth, Vascular - pathology</topic><topic>Neointima - pathology</topic><topic>Neointima - prevention & control</topic><topic>Propionates - administration & dosage</topic><topic>Propionates - pharmacology</topic><topic>Propionates - therapeutic use</topic><topic>Stents</topic><topic>Swine</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ialenti, Armando</creatorcontrib><creatorcontrib>Grassia, Gianluca</creatorcontrib><creatorcontrib>Gordon, Peter</creatorcontrib><creatorcontrib>Maddaluno, Marcella</creatorcontrib><creatorcontrib>Di Lauro, Maria Vittoria</creatorcontrib><creatorcontrib>Baker, Andrew H</creatorcontrib><creatorcontrib>Guglielmotti, Angelo</creatorcontrib><creatorcontrib>Colombo, Antonio</creatorcontrib><creatorcontrib>Biondi, Giuseppe</creatorcontrib><creatorcontrib>Kennedy, Simon</creatorcontrib><creatorcontrib>Maffia, Pasquale</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>Ialenti, Armando</au><au>Grassia, Gianluca</au><au>Gordon, Peter</au><au>Maddaluno, Marcella</au><au>Di Lauro, Maria Vittoria</au><au>Baker, Andrew H</au><au>Guglielmotti, Angelo</au><au>Colombo, Antonio</au><au>Biondi, Giuseppe</au><au>Kennedy, Simon</au><au>Maffia, Pasquale</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of In-Stent Stenosis by Oral Administration of Bindarit in Porcine Coronary Arteries</atitle><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle><addtitle>Arterioscler Thromb Vasc Biol</addtitle><date>2011-11</date><risdate>2011</risdate><volume>31</volume><issue>11</issue><spage>2448</spage><epage>2454</epage><pages>2448-2454</pages><issn>1079-5642</issn><eissn>1524-4636</eissn><coden>ATVBFA</coden><abstract><![CDATA[OBJECTIVE—We have previously demonstrated that bindarit, a selective inhibitor of monocyte chemotactic proteins (MCPs), is effective in reducing neointimal formation in rodent models of vascular injury by reducing smooth muscle cell proliferation and migration and neointimal macrophage content, effects associated with the inhibition of MCP-1/CCL2 production. The aim of the current study was to evaluate the efficacy of bindarit on in-stent stenosis in the preclinical porcine coronary stent model.
METHODS AND RESULTS—One or 2 bare metal stents (Multi-Link Vision, 3.5 mm) were deployed (1:1.2 oversize ratio) in the coronary arteries of 42 pigs (20 bindarit versus 22 controls). Bindarit (50 mg/kg per day) was administered orally from 2 days before stenting until the time of euthanasia at 7 and 28 days. Bindarit caused a significant reduction in neointimal area (39.4%, P<0.001, n=9 group), neointimal thickness (51%, P<0.001), stenosis area (37%, P<0.001), and inflammatory score (40%, P<0.001) compared with control animals, whereas there was no significant difference in the injury score between the 2 groups. Moreover, treatment with bindarit significantly reduced the number of proliferating cells (by 45%, P<0.05; n=6 group) and monocyte/macrophage content (by 55%, P<0.01; n=5–6 group) in stented arteries at day 7 and 28, respectively. These effects were associated with a significant (P<0.05) reduction of MCP-1 plasma levels at day 28. In vitro data showed that bindarit (10–300 μmol/L) reduced tumor necrosis factor-α (50 ng/mL)–induced pig coronary artery smooth muscle cell proliferation and inhibited MCP-1 production.
CONCLUSION—Our results show the efficacy of bindarit in the prevention of porcine in-stent stenosis and support further investigation for clinical application of this compound.]]></abstract><cop>Philadelphia, PA</cop><pub>American Heart Association, Inc</pub><pmid>21852559</pmid><doi>10.1161/ATVBAHA.111.230078</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Arteriosclerosis, thrombosis, and vascular biology, 2011-11, Vol.31 (11), p.2448-2454 |
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| subjects | Administration, Oral Animals Atherosclerosis (general aspects, experimental research) Biological and medical sciences Blood and lymphatic vessels Cardiology. Vascular system Cell Proliferation - drug effects Coronary heart disease Coronary Stenosis - pathology Coronary Stenosis - prevention & control Coronary Vessels - drug effects Coronary Vessels - pathology Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous Heart Indazoles - administration & dosage Indazoles - pharmacology Indazoles - therapeutic use Male Medical sciences Models, Animal Monocyte Chemoattractant Proteins - antagonists & inhibitors Monocyte Chemoattractant Proteins - blood Muscle, Smooth, Vascular - drug effects Muscle, Smooth, Vascular - pathology Neointima - pathology Neointima - prevention & control Propionates - administration & dosage Propionates - pharmacology Propionates - therapeutic use Stents Swine Treatment Outcome |
| title | Inhibition of In-Stent Stenosis by Oral Administration of Bindarit in Porcine Coronary Arteries |
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