A selective somatostatin type-2 receptor agonist inhibits neointimal thickening and enhances endothelial cell growth and morphology following aortic balloon injury in the rabbit
Somatostatin analogs have been shown to inhibit vascular smooth muscle cell (VSMC) proliferation and attenuate neointimal thickening following experimental balloon catheter injury. In this study, the effects of a selective agonist for the somatostatin receptor subtype 2, PRL-2486, on neointimal thic...
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| Veröffentlicht in: | Molecular and cellular biochemistry 2002-11, Vol.240 (1-2), p.31-37 |
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| creator | Schiller, Natalie K Timothy, Alvin M Aurora, Harmeet S Chen, I-Li Coy, David H Murphy, William A Akers, Donald L Fonseca, Vivian A Kadowitz, Philip J McNamara, Dennis B |
| description | Somatostatin analogs have been shown to inhibit vascular smooth muscle cell (VSMC) proliferation and attenuate neointimal thickening following experimental balloon catheter injury. In this study, the effects of a selective agonist for the somatostatin receptor subtype 2, PRL-2486, on neointimal thickening and endothelial cell regrowth 2 weeks following balloon catheterization of male New Zealand White rabbits were determined. Rabbits treated 2 days prior to and 2 weeks after catheter injury with 10 microg/kg/day PRL-2486 (PRL-tx) had decreased I/M ratios (intimal area/medial area x 100; p < 0.05) but had no effect at lower (5 microg/kg/day) or higher (20 microg/kg/day) doses. PRL-tx had significantly decreased VSMC proliferation compared to untreated animals. PRL-tx increased endothelial regrowth by over 2-fold (p < 0.002) and improved endothelial cell morphology. Endothelial-dependent relaxation responses to acetylcholine were attenuated by catheter injury, and were not improved with PRL-tx. These data suggest that the PRL-2486-mediated inhibition of neointimal thickening exhibits a bell-shaped dose-response curve. This inhibition may be due in part to decreased VSMC proliferation, which may be a function of enhanced endothelial regrowth, but not the return of endothelium-dependent vascular function. |
| doi_str_mv | 10.1023/A:1020679809056 |
| format | Article |
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In this study, the effects of a selective agonist for the somatostatin receptor subtype 2, PRL-2486, on neointimal thickening and endothelial cell regrowth 2 weeks following balloon catheterization of male New Zealand White rabbits were determined. Rabbits treated 2 days prior to and 2 weeks after catheter injury with 10 microg/kg/day PRL-2486 (PRL-tx) had decreased I/M ratios (intimal area/medial area x 100; p < 0.05) but had no effect at lower (5 microg/kg/day) or higher (20 microg/kg/day) doses. PRL-tx had significantly decreased VSMC proliferation compared to untreated animals. PRL-tx increased endothelial regrowth by over 2-fold (p < 0.002) and improved endothelial cell morphology. Endothelial-dependent relaxation responses to acetylcholine were attenuated by catheter injury, and were not improved with PRL-tx. These data suggest that the PRL-2486-mediated inhibition of neointimal thickening exhibits a bell-shaped dose-response curve. This inhibition may be due in part to decreased VSMC proliferation, which may be a function of enhanced endothelial regrowth, but not the return of endothelium-dependent vascular function.</description><identifier>ISSN: 0300-8177</identifier><identifier>EISSN: 1573-4919</identifier><identifier>DOI: 10.1023/A:1020679809056</identifier><identifier>PMID: 12487369</identifier><language>eng</language><publisher>Netherlands: Springer Nature B.V</publisher><subject>Animals ; Aorta - injuries ; Aorta - pathology ; Aorta - ultrastructure ; Catheterization - adverse effects ; Cell Division - drug effects ; Cell morphology ; Cell Size - drug effects ; Cells ; Disease Models, Animal ; Endothelium, Vascular - drug effects ; Endothelium, Vascular - injuries ; Endothelium, Vascular - pathology ; Male ; Medical instruments ; Microscopy, Electron ; Muscular system ; Rabbits ; Receptors, Somatostatin - agonists ; Regrowth ; Sensitivity and Specificity ; Tunica Intima - drug effects ; Tunica Intima - injuries ; Tunica Intima - pathology</subject><ispartof>Molecular and cellular biochemistry, 2002-11, Vol.240 (1-2), p.31-37</ispartof><rights>Kluwer Academic Publishers 2002</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c280t-6018a0bdbaa9aea5c7bd08183a35e70d36e2090c71a6eaf6465db11c6c56a0893</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,27911,27912</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12487369$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schiller, Natalie K</creatorcontrib><creatorcontrib>Timothy, Alvin M</creatorcontrib><creatorcontrib>Aurora, Harmeet S</creatorcontrib><creatorcontrib>Chen, I-Li</creatorcontrib><creatorcontrib>Coy, David H</creatorcontrib><creatorcontrib>Murphy, William A</creatorcontrib><creatorcontrib>Akers, Donald L</creatorcontrib><creatorcontrib>Fonseca, Vivian A</creatorcontrib><creatorcontrib>Kadowitz, Philip J</creatorcontrib><creatorcontrib>McNamara, Dennis B</creatorcontrib><title>A selective somatostatin type-2 receptor agonist inhibits neointimal thickening and enhances endothelial cell growth and morphology following aortic balloon injury in the rabbit</title><title>Molecular and cellular biochemistry</title><addtitle>Mol Cell Biochem</addtitle><description>Somatostatin analogs have been shown to inhibit vascular smooth muscle cell (VSMC) proliferation and attenuate neointimal thickening following experimental balloon catheter injury. In this study, the effects of a selective agonist for the somatostatin receptor subtype 2, PRL-2486, on neointimal thickening and endothelial cell regrowth 2 weeks following balloon catheterization of male New Zealand White rabbits were determined. Rabbits treated 2 days prior to and 2 weeks after catheter injury with 10 microg/kg/day PRL-2486 (PRL-tx) had decreased I/M ratios (intimal area/medial area x 100; p < 0.05) but had no effect at lower (5 microg/kg/day) or higher (20 microg/kg/day) doses. PRL-tx had significantly decreased VSMC proliferation compared to untreated animals. PRL-tx increased endothelial regrowth by over 2-fold (p < 0.002) and improved endothelial cell morphology. Endothelial-dependent relaxation responses to acetylcholine were attenuated by catheter injury, and were not improved with PRL-tx. These data suggest that the PRL-2486-mediated inhibition of neointimal thickening exhibits a bell-shaped dose-response curve. This inhibition may be due in part to decreased VSMC proliferation, which may be a function of enhanced endothelial regrowth, but not the return of endothelium-dependent vascular function.</description><subject>Animals</subject><subject>Aorta - injuries</subject><subject>Aorta - pathology</subject><subject>Aorta - ultrastructure</subject><subject>Catheterization - adverse effects</subject><subject>Cell Division - drug effects</subject><subject>Cell morphology</subject><subject>Cell Size - drug effects</subject><subject>Cells</subject><subject>Disease Models, Animal</subject><subject>Endothelium, Vascular - drug effects</subject><subject>Endothelium, Vascular - injuries</subject><subject>Endothelium, Vascular - pathology</subject><subject>Male</subject><subject>Medical instruments</subject><subject>Microscopy, Electron</subject><subject>Muscular system</subject><subject>Rabbits</subject><subject>Receptors, Somatostatin - agonists</subject><subject>Regrowth</subject><subject>Sensitivity and Specificity</subject><subject>Tunica Intima - 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Academic</collection><jtitle>Molecular and cellular biochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schiller, Natalie K</au><au>Timothy, Alvin M</au><au>Aurora, Harmeet S</au><au>Chen, I-Li</au><au>Coy, David H</au><au>Murphy, William A</au><au>Akers, Donald L</au><au>Fonseca, Vivian A</au><au>Kadowitz, Philip J</au><au>McNamara, Dennis B</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A selective somatostatin type-2 receptor agonist inhibits neointimal thickening and enhances endothelial cell growth and morphology following aortic balloon injury in the rabbit</atitle><jtitle>Molecular and cellular biochemistry</jtitle><addtitle>Mol Cell Biochem</addtitle><date>2002-11</date><risdate>2002</risdate><volume>240</volume><issue>1-2</issue><spage>31</spage><epage>37</epage><pages>31-37</pages><issn>0300-8177</issn><eissn>1573-4919</eissn><abstract>Somatostatin analogs have been shown to inhibit vascular smooth muscle cell (VSMC) proliferation and attenuate neointimal thickening following experimental balloon catheter injury. In this study, the effects of a selective agonist for the somatostatin receptor subtype 2, PRL-2486, on neointimal thickening and endothelial cell regrowth 2 weeks following balloon catheterization of male New Zealand White rabbits were determined. Rabbits treated 2 days prior to and 2 weeks after catheter injury with 10 microg/kg/day PRL-2486 (PRL-tx) had decreased I/M ratios (intimal area/medial area x 100; p < 0.05) but had no effect at lower (5 microg/kg/day) or higher (20 microg/kg/day) doses. PRL-tx had significantly decreased VSMC proliferation compared to untreated animals. PRL-tx increased endothelial regrowth by over 2-fold (p < 0.002) and improved endothelial cell morphology. Endothelial-dependent relaxation responses to acetylcholine were attenuated by catheter injury, and were not improved with PRL-tx. These data suggest that the PRL-2486-mediated inhibition of neointimal thickening exhibits a bell-shaped dose-response curve. This inhibition may be due in part to decreased VSMC proliferation, which may be a function of enhanced endothelial regrowth, but not the return of endothelium-dependent vascular function.</abstract><cop>Netherlands</cop><pub>Springer Nature B.V</pub><pmid>12487369</pmid><doi>10.1023/A:1020679809056</doi><tpages>7</tpages></addata></record> |
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| ispartof | Molecular and cellular biochemistry, 2002-11, Vol.240 (1-2), p.31-37 |
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| subjects | Animals Aorta - injuries Aorta - pathology Aorta - ultrastructure Catheterization - adverse effects Cell Division - drug effects Cell morphology Cell Size - drug effects Cells Disease Models, Animal Endothelium, Vascular - drug effects Endothelium, Vascular - injuries Endothelium, Vascular - pathology Male Medical instruments Microscopy, Electron Muscular system Rabbits Receptors, Somatostatin - agonists Regrowth Sensitivity and Specificity Tunica Intima - drug effects Tunica Intima - injuries Tunica Intima - pathology |
| title | A selective somatostatin type-2 receptor agonist inhibits neointimal thickening and enhances endothelial cell growth and morphology following aortic balloon injury in the rabbit |
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