MicroRNA-145-loaded poly(lactic-co-glycolic acid) nanoparticles attenuate venous intimal hyperplasia in a rabbit model
MicroRNA-145 (miR-145) reportedly alters the phenotype of vascular smooth muscle cells (VSMCs) from a proliferative to a contractile state. So far, viral or plasmid vectors have been experimentally used to transduce microRNAs into VSMCs. We hypothesized that a simple ex vivo microRNA delivery system...
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| Veröffentlicht in: | The Journal of thoracic and cardiovascular surgery 2019-06, Vol.157 (6), p.2242-2251 |
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| container_title | The Journal of thoracic and cardiovascular surgery |
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| creator | Nishio, Hiroomi Masumoto, Hidetoshi Sakamoto, Kazuhisa Yamazaki, Kazuhiro Ikeda, Tadashi Minatoya, Kenji |
| description | MicroRNA-145 (miR-145) reportedly alters the phenotype of vascular smooth muscle cells (VSMCs) from a proliferative to a contractile state. So far, viral or plasmid vectors have been experimentally used to transduce microRNAs into VSMCs. We hypothesized that a simple ex vivo microRNA delivery system using miR–145-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (PLGA NPs) could control the VSMC phenotype and prevent intimal hyperplasia.
Jugular vein grafts of male Japanese white rabbits were soaked in phosphate-buffered saline, control microRNA (cont-miR)-loaded PLGA NP solution or miR–145-loaded PLGA NP solution for 30 minutes (n = 8 for each). Vein grafts were implanted in the ipsilateral carotid artery and assessed 2 weeks after the implantation.
Quantitative polymerase chain reaction analysis showed significantly higher miR-145 expression in the miR–145-treated group. The neointimal area was significantly smaller in the miR–145-treated group (phosphate-buffered saline-treated vs cont–miR-treated vs miR–145-treated group; 1.63 ± 0.52 mm2 vs 1.67 ± 0.49 mm2 vs 0.88 ± 0.34 mm2, respectively; P |
| doi_str_mv | 10.1016/j.jtcvs.2018.08.115 |
| format | Article |
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Jugular vein grafts of male Japanese white rabbits were soaked in phosphate-buffered saline, control microRNA (cont-miR)-loaded PLGA NP solution or miR–145-loaded PLGA NP solution for 30 minutes (n = 8 for each). Vein grafts were implanted in the ipsilateral carotid artery and assessed 2 weeks after the implantation.
Quantitative polymerase chain reaction analysis showed significantly higher miR-145 expression in the miR–145-treated group. The neointimal area was significantly smaller in the miR–145-treated group (phosphate-buffered saline-treated vs cont–miR-treated vs miR–145-treated group; 1.63 ± 0.52 mm2 vs 1.67 ± 0.49 mm2 vs 0.88 ± 0.34 mm2, respectively; P < .01 for the miR–145-treated vs the cont–miR-treated group). In the miR–145-treated group, Ki–67-positive cells were significantly fewer, indicating lower VSMC proliferation. An inflammation-related molecule, CD40 expression was significantly reduced by miR–145-loaded PLGA NP treatment.
Local and sustained release of miR-145 by PLGA NPs attenuated intimal hyperplasia in the rabbit model by maintaining VSMCs in a contractile state. This simple ex vivo miR-145 delivery system would be promising toward broader clinical application.
[Display omitted]</description><identifier>ISSN: 0022-5223</identifier><identifier>EISSN: 1097-685X</identifier><identifier>DOI: 10.1016/j.jtcvs.2018.08.115</identifier><identifier>PMID: 30447962</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Disease Models, Animal ; drug delivery system ; Hyperplasia - drug therapy ; Hyperplasia - pathology ; Male ; microRNA ; MicroRNAs - therapeutic use ; Muscle, Smooth, Vascular - drug effects ; Muscle, Smooth, Vascular - pathology ; Nanoparticles - therapeutic use ; Polylactic Acid-Polyglycolic Acid Copolymer - therapeutic use ; Rabbits ; Tunica Intima - drug effects ; Tunica Intima - pathology ; vein graft</subject><ispartof>The Journal of thoracic and cardiovascular surgery, 2019-06, Vol.157 (6), p.2242-2251</ispartof><rights>2018 The American Association for Thoracic Surgery</rights><rights>Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c470t-1b6bc1b3dc876416b3a1ca8174951b63e6405c84799f2396e8f09618a18711053</citedby><cites>FETCH-LOGICAL-c470t-1b6bc1b3dc876416b3a1ca8174951b63e6405c84799f2396e8f09618a18711053</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0022522318325157$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30447962$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nishio, Hiroomi</creatorcontrib><creatorcontrib>Masumoto, Hidetoshi</creatorcontrib><creatorcontrib>Sakamoto, Kazuhisa</creatorcontrib><creatorcontrib>Yamazaki, Kazuhiro</creatorcontrib><creatorcontrib>Ikeda, Tadashi</creatorcontrib><creatorcontrib>Minatoya, Kenji</creatorcontrib><title>MicroRNA-145-loaded poly(lactic-co-glycolic acid) nanoparticles attenuate venous intimal hyperplasia in a rabbit model</title><title>The Journal of thoracic and cardiovascular surgery</title><addtitle>J Thorac Cardiovasc Surg</addtitle><description>MicroRNA-145 (miR-145) reportedly alters the phenotype of vascular smooth muscle cells (VSMCs) from a proliferative to a contractile state. So far, viral or plasmid vectors have been experimentally used to transduce microRNAs into VSMCs. We hypothesized that a simple ex vivo microRNA delivery system using miR–145-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (PLGA NPs) could control the VSMC phenotype and prevent intimal hyperplasia.
Jugular vein grafts of male Japanese white rabbits were soaked in phosphate-buffered saline, control microRNA (cont-miR)-loaded PLGA NP solution or miR–145-loaded PLGA NP solution for 30 minutes (n = 8 for each). Vein grafts were implanted in the ipsilateral carotid artery and assessed 2 weeks after the implantation.
Quantitative polymerase chain reaction analysis showed significantly higher miR-145 expression in the miR–145-treated group. The neointimal area was significantly smaller in the miR–145-treated group (phosphate-buffered saline-treated vs cont–miR-treated vs miR–145-treated group; 1.63 ± 0.52 mm2 vs 1.67 ± 0.49 mm2 vs 0.88 ± 0.34 mm2, respectively; P < .01 for the miR–145-treated vs the cont–miR-treated group). In the miR–145-treated group, Ki–67-positive cells were significantly fewer, indicating lower VSMC proliferation. An inflammation-related molecule, CD40 expression was significantly reduced by miR–145-loaded PLGA NP treatment.
Local and sustained release of miR-145 by PLGA NPs attenuated intimal hyperplasia in the rabbit model by maintaining VSMCs in a contractile state. This simple ex vivo miR-145 delivery system would be promising toward broader clinical application.
[Display omitted]</description><subject>Animals</subject><subject>Disease Models, Animal</subject><subject>drug delivery system</subject><subject>Hyperplasia - drug therapy</subject><subject>Hyperplasia - pathology</subject><subject>Male</subject><subject>microRNA</subject><subject>MicroRNAs - therapeutic use</subject><subject>Muscle, Smooth, Vascular - drug effects</subject><subject>Muscle, Smooth, Vascular - pathology</subject><subject>Nanoparticles - therapeutic use</subject><subject>Polylactic Acid-Polyglycolic Acid Copolymer - therapeutic use</subject><subject>Rabbits</subject><subject>Tunica Intima - drug effects</subject><subject>Tunica Intima - pathology</subject><subject>vein graft</subject><issn>0022-5223</issn><issn>1097-685X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE-LFDEQxYMo7rj6CQTJcT2krep0p9MHD8viP1gVRMFbSKdrNEOm0yaZgfn2Zp3Vo6eCqveq6v0Ye47QIKB6tWt2xR1z0wLqBnSD2D9gG4RxEEr33x-yDUDbir5t5QV7kvMOAAbA8TG7kNB1w6jaDTt-9C7FL5-uBXa9CNHONPM1htNVsK54J1wUP8LJxeAdt87PL_lil7jaVIeBMrel0HKwhfiRlnjI3C_F723gP08rpTXY7G3tccuTnSZf-D7OFJ6yR1sbMj27r5fs29s3X2_ei9vP7z7cXN8K1w1QBE5qcjjJ2elBdagmadFZjUM39nUmSXXQO12zjNtWjor0FkaF2qIeEKGXl-zqvHdN8deBcjF7nx2FYBeqz5oWZa9kL_VYpfIsrTxyTrQ1a6pB0skgmDvgZmf-ADd3wA1oU4FX14v7A4dpT_M_z1_CVfD6LKAa8-gpmew8LY5mn8gVM0f_3wO_AfqIkqI</recordid><startdate>201906</startdate><enddate>201906</enddate><creator>Nishio, Hiroomi</creator><creator>Masumoto, Hidetoshi</creator><creator>Sakamoto, Kazuhisa</creator><creator>Yamazaki, Kazuhiro</creator><creator>Ikeda, Tadashi</creator><creator>Minatoya, Kenji</creator><general>Elsevier 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>201906</creationdate><title>MicroRNA-145-loaded poly(lactic-co-glycolic acid) nanoparticles attenuate venous intimal hyperplasia in a rabbit model</title><author>Nishio, Hiroomi ; Masumoto, Hidetoshi ; Sakamoto, Kazuhisa ; Yamazaki, Kazuhiro ; Ikeda, Tadashi ; Minatoya, Kenji</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c470t-1b6bc1b3dc876416b3a1ca8174951b63e6405c84799f2396e8f09618a18711053</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>Disease Models, Animal</topic><topic>drug delivery system</topic><topic>Hyperplasia - drug therapy</topic><topic>Hyperplasia - pathology</topic><topic>Male</topic><topic>microRNA</topic><topic>MicroRNAs - therapeutic use</topic><topic>Muscle, Smooth, Vascular - drug effects</topic><topic>Muscle, Smooth, Vascular - pathology</topic><topic>Nanoparticles - therapeutic use</topic><topic>Polylactic Acid-Polyglycolic Acid Copolymer - therapeutic use</topic><topic>Rabbits</topic><topic>Tunica Intima - drug effects</topic><topic>Tunica Intima - pathology</topic><topic>vein graft</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nishio, Hiroomi</creatorcontrib><creatorcontrib>Masumoto, Hidetoshi</creatorcontrib><creatorcontrib>Sakamoto, Kazuhisa</creatorcontrib><creatorcontrib>Yamazaki, Kazuhiro</creatorcontrib><creatorcontrib>Ikeda, Tadashi</creatorcontrib><creatorcontrib>Minatoya, Kenji</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>The Journal of thoracic and cardiovascular surgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nishio, Hiroomi</au><au>Masumoto, Hidetoshi</au><au>Sakamoto, Kazuhisa</au><au>Yamazaki, Kazuhiro</au><au>Ikeda, Tadashi</au><au>Minatoya, Kenji</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MicroRNA-145-loaded poly(lactic-co-glycolic acid) nanoparticles attenuate venous intimal hyperplasia in a rabbit model</atitle><jtitle>The Journal of thoracic and cardiovascular surgery</jtitle><addtitle>J Thorac Cardiovasc Surg</addtitle><date>2019-06</date><risdate>2019</risdate><volume>157</volume><issue>6</issue><spage>2242</spage><epage>2251</epage><pages>2242-2251</pages><issn>0022-5223</issn><eissn>1097-685X</eissn><abstract>MicroRNA-145 (miR-145) reportedly alters the phenotype of vascular smooth muscle cells (VSMCs) from a proliferative to a contractile state. So far, viral or plasmid vectors have been experimentally used to transduce microRNAs into VSMCs. We hypothesized that a simple ex vivo microRNA delivery system using miR–145-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (PLGA NPs) could control the VSMC phenotype and prevent intimal hyperplasia.
Jugular vein grafts of male Japanese white rabbits were soaked in phosphate-buffered saline, control microRNA (cont-miR)-loaded PLGA NP solution or miR–145-loaded PLGA NP solution for 30 minutes (n = 8 for each). Vein grafts were implanted in the ipsilateral carotid artery and assessed 2 weeks after the implantation.
Quantitative polymerase chain reaction analysis showed significantly higher miR-145 expression in the miR–145-treated group. The neointimal area was significantly smaller in the miR–145-treated group (phosphate-buffered saline-treated vs cont–miR-treated vs miR–145-treated group; 1.63 ± 0.52 mm2 vs 1.67 ± 0.49 mm2 vs 0.88 ± 0.34 mm2, respectively; P < .01 for the miR–145-treated vs the cont–miR-treated group). In the miR–145-treated group, Ki–67-positive cells were significantly fewer, indicating lower VSMC proliferation. An inflammation-related molecule, CD40 expression was significantly reduced by miR–145-loaded PLGA NP treatment.
Local and sustained release of miR-145 by PLGA NPs attenuated intimal hyperplasia in the rabbit model by maintaining VSMCs in a contractile state. This simple ex vivo miR-145 delivery system would be promising toward broader clinical application.
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| subjects | Animals Disease Models, Animal drug delivery system Hyperplasia - drug therapy Hyperplasia - pathology Male microRNA MicroRNAs - therapeutic use Muscle, Smooth, Vascular - drug effects Muscle, Smooth, Vascular - pathology Nanoparticles - therapeutic use Polylactic Acid-Polyglycolic Acid Copolymer - therapeutic use Rabbits Tunica Intima - drug effects Tunica Intima - pathology vein graft |
| title | MicroRNA-145-loaded poly(lactic-co-glycolic acid) nanoparticles attenuate venous intimal hyperplasia in a rabbit model |
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