The herbal extract HMC05 inhibits neointima formation in balloon-injured rat carotid arteries: Possible therapeutic implications of HMC05
In a previous study, HMC05, a water extract from eight medicinal herbs was demonstrated to possess anti-inflammatory effects in murine macrophages and anti-atherosclerotic effects in apoE −/− mice. HSP27 expression was shown to be decreased in advanced atherosclerotic plaques of human carotid arteri...
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description | In a previous study, HMC05, a water extract from eight medicinal herbs was demonstrated to possess anti-inflammatory effects in murine macrophages and anti-atherosclerotic effects in apoE
−/− mice. HSP27 expression was shown to be decreased in advanced atherosclerotic plaques of human carotid arteries. In the present study, the role of HMC05 in the prevention of restenosis and the possible mechanisms involved in the decrease of neointima formation were investigated using
in vivo balloon injury rat model and
in vitro biochemical assays.
A rat carotid artery balloon injury restenosis model was used. Different doses of HMC05 were administered to the rats by tube feeding, starting from four days before surgery and continuing twice per week for two weeks after carotid injury. Injured carotid arteries isolated from rats were embedded in paraffin block and tissue sections were stained with H&E to assess neointima formation. Mechanism by HMC05 that are involved in smooth muscle cell proliferation and migration was assessed by western blot assay, immunohistochemistry and confocal analysis.
There was no significant difference in the medial area between the control and HMC05-treated groups. However, neointima formation was significantly inhibited in the HMC05-treated group, resulting in 47-fold lower intima to media ratios in rats treated with 25
mg/kg/day HMC05 as compared to the control. Surprisingly, monocytes infiltration in the neointima area was almost completely blocked by HMC05 administration. When rat vascular SMCs were treated with HMC05, the proliferation and migration of smooth muscle cells was dramatically inhibited in a dye uptake assay and in a scratch model in a culture dish, respectively. HMC05 dose-dependently inhibited PDGF-mediated MAPK and AKT activation. However, HMC05 did not affect PDGF-mediated HSP27 phosphorylation but it induced HSP27 overexpression and phosphorylation. In addition, medial SMCs in the arterial wall of rats treated with HMC05 showed a significant increase in HSP27 expression compared with that of the control rats.
HMC05, a strong anti-inflammatory reagent, might use HSP27 as an effector molecule in SMCs to reduce neointimal hyperplasia by inhibiting PDGF-mediated MAPK and AKT activation. HMC05 could be a useful drug candidate for the prevention of restenosis after balloon injury of the arteries. |
doi_str_mv | 10.1016/j.jep.2010.09.015 |
format | Article |
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−/− mice. HSP27 expression was shown to be decreased in advanced atherosclerotic plaques of human carotid arteries. In the present study, the role of HMC05 in the prevention of restenosis and the possible mechanisms involved in the decrease of neointima formation were investigated using
in vivo balloon injury rat model and
in vitro biochemical assays.
A rat carotid artery balloon injury restenosis model was used. Different doses of HMC05 were administered to the rats by tube feeding, starting from four days before surgery and continuing twice per week for two weeks after carotid injury. Injured carotid arteries isolated from rats were embedded in paraffin block and tissue sections were stained with H&E to assess neointima formation. Mechanism by HMC05 that are involved in smooth muscle cell proliferation and migration was assessed by western blot assay, immunohistochemistry and confocal analysis.
There was no significant difference in the medial area between the control and HMC05-treated groups. However, neointima formation was significantly inhibited in the HMC05-treated group, resulting in 47-fold lower intima to media ratios in rats treated with 25
mg/kg/day HMC05 as compared to the control. Surprisingly, monocytes infiltration in the neointima area was almost completely blocked by HMC05 administration. When rat vascular SMCs were treated with HMC05, the proliferation and migration of smooth muscle cells was dramatically inhibited in a dye uptake assay and in a scratch model in a culture dish, respectively. HMC05 dose-dependently inhibited PDGF-mediated MAPK and AKT activation. However, HMC05 did not affect PDGF-mediated HSP27 phosphorylation but it induced HSP27 overexpression and phosphorylation. In addition, medial SMCs in the arterial wall of rats treated with HMC05 showed a significant increase in HSP27 expression compared with that of the control rats.
HMC05, a strong anti-inflammatory reagent, might use HSP27 as an effector molecule in SMCs to reduce neointimal hyperplasia by inhibiting PDGF-mediated MAPK and AKT activation. HMC05 could be a useful drug candidate for the prevention of restenosis after balloon injury of the arteries.</description><identifier>ISSN: 0378-8741</identifier><identifier>EISSN: 1872-7573</identifier><identifier>DOI: 10.1016/j.jep.2010.09.015</identifier><identifier>PMID: 20883768</identifier><identifier>CODEN: JOETD7</identifier><language>eng</language><publisher>Shannon: Elsevier Ireland Ltd</publisher><subject>animal models ; animal tissues ; Animals ; Anti-Inflammatory Agents - pharmacology ; arterial intima ; atherosclerosis ; Balloon injury model ; biochemical pathways ; Biological and medical sciences ; blood flow ; carotid arteries ; Carotid Arteries - drug effects ; Carotid Arteries - metabolism ; Carotid Artery Injuries - pathology ; Catheterization ; cell migration ; Cell Movement - drug effects ; cell proliferation ; Cell Proliferation - drug effects ; Cells, Cultured ; Coronary Restenosis - prevention & control ; Disease Models, Animal ; dosage ; dose response ; drug formulations ; General pharmacology ; Herb ; herbal medicines ; histopathology ; HMC05 ; HSP27 Heat-Shock Proteins - metabolism ; Humans ; hyperplasia ; immunohistochemistry ; in vitro studies ; in vivo studies ; inflammation ; Male ; mechanism of action ; Medical sciences ; medicinal plants ; Mice ; Muscle, Smooth, Vascular - drug effects ; Muscle, Smooth, Vascular - metabolism ; Muscle, Smooth, Vascular - pathology ; Neointima - prevention & control ; neointima formation ; Neointimal hyperplasia ; oral administration ; Pharmacognosy. Homeopathy. Health food ; Pharmacology. Drug treatments ; Phytotherapy ; plant extracts ; Plant Extracts - pharmacology ; Plants, Medicinal ; Plaque, Atherosclerotic - pathology ; Plaque, Atherosclerotic - prevention & control ; Platelet-Derived Growth Factor - metabolism ; Proto-Oncogene Proteins c-sis ; Rats ; Restenosis ; Signal Transduction ; smooth muscle ; stenosis</subject><ispartof>Journal of ethnopharmacology, 2011-01, Vol.133 (1), p.168-176</ispartof><rights>2010 Elsevier Ireland Ltd</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c472t-1ba1b14ce4aa823f0073d7310389ec1766e2e7b704dec57d749b3c536ef16f7f3</citedby><cites>FETCH-LOGICAL-c472t-1ba1b14ce4aa823f0073d7310389ec1766e2e7b704dec57d749b3c536ef16f7f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0378874110006562$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23817499$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20883768$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Jo Woon Yi</creatorcontrib><creatorcontrib>Lee, Bok-Soo</creatorcontrib><creatorcontrib>Lee, Ji Yeun</creatorcontrib><creatorcontrib>Ku, Hyo Jung</creatorcontrib><creatorcontrib>Jeon, So-Ra</creatorcontrib><creatorcontrib>Kim, Joo Yun</creatorcontrib><creatorcontrib>Ban, Ji Min</creatorcontrib><creatorcontrib>Sung, Sang Hyun</creatorcontrib><creatorcontrib>Shin, Heung Mook</creatorcontrib><creatorcontrib>Park, Jeong Euy</creatorcontrib><title>The herbal extract HMC05 inhibits neointima formation in balloon-injured rat carotid arteries: Possible therapeutic implications of HMC05</title><title>Journal of ethnopharmacology</title><addtitle>J Ethnopharmacol</addtitle><description>In a previous study, HMC05, a water extract from eight medicinal herbs was demonstrated to possess anti-inflammatory effects in murine macrophages and anti-atherosclerotic effects in apoE
−/− mice. HSP27 expression was shown to be decreased in advanced atherosclerotic plaques of human carotid arteries. In the present study, the role of HMC05 in the prevention of restenosis and the possible mechanisms involved in the decrease of neointima formation were investigated using
in vivo balloon injury rat model and
in vitro biochemical assays.
A rat carotid artery balloon injury restenosis model was used. Different doses of HMC05 were administered to the rats by tube feeding, starting from four days before surgery and continuing twice per week for two weeks after carotid injury. Injured carotid arteries isolated from rats were embedded in paraffin block and tissue sections were stained with H&E to assess neointima formation. Mechanism by HMC05 that are involved in smooth muscle cell proliferation and migration was assessed by western blot assay, immunohistochemistry and confocal analysis.
There was no significant difference in the medial area between the control and HMC05-treated groups. However, neointima formation was significantly inhibited in the HMC05-treated group, resulting in 47-fold lower intima to media ratios in rats treated with 25
mg/kg/day HMC05 as compared to the control. Surprisingly, monocytes infiltration in the neointima area was almost completely blocked by HMC05 administration. When rat vascular SMCs were treated with HMC05, the proliferation and migration of smooth muscle cells was dramatically inhibited in a dye uptake assay and in a scratch model in a culture dish, respectively. HMC05 dose-dependently inhibited PDGF-mediated MAPK and AKT activation. However, HMC05 did not affect PDGF-mediated HSP27 phosphorylation but it induced HSP27 overexpression and phosphorylation. In addition, medial SMCs in the arterial wall of rats treated with HMC05 showed a significant increase in HSP27 expression compared with that of the control rats.
HMC05, a strong anti-inflammatory reagent, might use HSP27 as an effector molecule in SMCs to reduce neointimal hyperplasia by inhibiting PDGF-mediated MAPK and AKT activation. HMC05 could be a useful drug candidate for the prevention of restenosis after balloon injury of the arteries.</description><subject>animal models</subject><subject>animal tissues</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>arterial intima</subject><subject>atherosclerosis</subject><subject>Balloon injury model</subject><subject>biochemical pathways</subject><subject>Biological and medical sciences</subject><subject>blood flow</subject><subject>carotid arteries</subject><subject>Carotid Arteries - drug effects</subject><subject>Carotid Arteries - metabolism</subject><subject>Carotid Artery Injuries - pathology</subject><subject>Catheterization</subject><subject>cell migration</subject><subject>Cell Movement - drug effects</subject><subject>cell proliferation</subject><subject>Cell Proliferation - drug effects</subject><subject>Cells, Cultured</subject><subject>Coronary Restenosis - prevention & control</subject><subject>Disease Models, Animal</subject><subject>dosage</subject><subject>dose response</subject><subject>drug formulations</subject><subject>General pharmacology</subject><subject>Herb</subject><subject>herbal medicines</subject><subject>histopathology</subject><subject>HMC05</subject><subject>HSP27 Heat-Shock Proteins - metabolism</subject><subject>Humans</subject><subject>hyperplasia</subject><subject>immunohistochemistry</subject><subject>in vitro studies</subject><subject>in vivo studies</subject><subject>inflammation</subject><subject>Male</subject><subject>mechanism of action</subject><subject>Medical sciences</subject><subject>medicinal plants</subject><subject>Mice</subject><subject>Muscle, Smooth, Vascular - drug effects</subject><subject>Muscle, Smooth, Vascular - metabolism</subject><subject>Muscle, Smooth, Vascular - pathology</subject><subject>Neointima - prevention & control</subject><subject>neointima formation</subject><subject>Neointimal hyperplasia</subject><subject>oral administration</subject><subject>Pharmacognosy. Homeopathy. Health food</subject><subject>Pharmacology. Drug treatments</subject><subject>Phytotherapy</subject><subject>plant extracts</subject><subject>Plant Extracts - pharmacology</subject><subject>Plants, Medicinal</subject><subject>Plaque, Atherosclerotic - pathology</subject><subject>Plaque, Atherosclerotic - prevention & control</subject><subject>Platelet-Derived Growth Factor - metabolism</subject><subject>Proto-Oncogene Proteins c-sis</subject><subject>Rats</subject><subject>Restenosis</subject><subject>Signal Transduction</subject><subject>smooth muscle</subject><subject>stenosis</subject><issn>0378-8741</issn><issn>1872-7573</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1u1TAQhSMEoreFB2AD3iBWufgniR1YoStKkYpAol1bjjPmOkriYDsIHoG3ZkousGNljfzNzJlziuIJo3tGWfNy2A-w7DnFmrZ7yup7xY4pyUtZS3G_2FEhValkxc6K85QGSqlkFX1YnHGqlJCN2hU_b45AjhA7MxL4nqOxmVx9ONCa-PnoO58TmSH4OfvJEBfiZLIPM34S7BhDmEs_D2uEnkSTiTUxZN8TEzNED-kV-RRS8t0IJOMSs8CavSV-WkZvf09KJLht4aPigTNjgsen96K4vXx7c7gqrz--e394c13aSvJcss6wjlUWKmMUFw5vEr0UjArVgmWyaYCD7CSterC17GXVdsLWogHHGieduChebHOXGL6ukLKefLIwjgYPXZNWnFWqFbxBkm2kjXhFBKeXiDbEH5pRfReAHjQGoO8C0LTVGAD2PD1NX7sJ-r8dfxxH4PkJMMma0UUzW5_-cUIxlNwi92zjnAnafInI3H7GTYKylqM6jsTrjQB065uHqJP1MFvofQSbdR_8f4T-Ar-HraI</recordid><startdate>20110107</startdate><enddate>20110107</enddate><creator>Lee, Jo Woon Yi</creator><creator>Lee, Bok-Soo</creator><creator>Lee, Ji Yeun</creator><creator>Ku, Hyo Jung</creator><creator>Jeon, So-Ra</creator><creator>Kim, Joo Yun</creator><creator>Ban, Ji Min</creator><creator>Sung, Sang Hyun</creator><creator>Shin, Heung Mook</creator><creator>Park, Jeong Euy</creator><general>Elsevier Ireland Ltd</general><general>Amsterdam; New York: Elsevier</general><general>Elsevier</general><scope>FBQ</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>20110107</creationdate><title>The herbal extract HMC05 inhibits neointima formation in balloon-injured rat carotid arteries: Possible therapeutic implications of HMC05</title><author>Lee, Jo Woon Yi ; Lee, Bok-Soo ; Lee, Ji Yeun ; Ku, Hyo Jung ; Jeon, So-Ra ; Kim, Joo Yun ; Ban, Ji Min ; Sung, Sang Hyun ; Shin, Heung Mook ; Park, Jeong Euy</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c472t-1ba1b14ce4aa823f0073d7310389ec1766e2e7b704dec57d749b3c536ef16f7f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>animal models</topic><topic>animal tissues</topic><topic>Animals</topic><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>arterial intima</topic><topic>atherosclerosis</topic><topic>Balloon injury model</topic><topic>biochemical pathways</topic><topic>Biological and medical sciences</topic><topic>blood flow</topic><topic>carotid arteries</topic><topic>Carotid Arteries - drug effects</topic><topic>Carotid Arteries - metabolism</topic><topic>Carotid Artery Injuries - pathology</topic><topic>Catheterization</topic><topic>cell migration</topic><topic>Cell Movement - drug effects</topic><topic>cell proliferation</topic><topic>Cell Proliferation - drug effects</topic><topic>Cells, Cultured</topic><topic>Coronary Restenosis - prevention & control</topic><topic>Disease Models, Animal</topic><topic>dosage</topic><topic>dose response</topic><topic>drug formulations</topic><topic>General pharmacology</topic><topic>Herb</topic><topic>herbal medicines</topic><topic>histopathology</topic><topic>HMC05</topic><topic>HSP27 Heat-Shock Proteins - metabolism</topic><topic>Humans</topic><topic>hyperplasia</topic><topic>immunohistochemistry</topic><topic>in vitro studies</topic><topic>in vivo studies</topic><topic>inflammation</topic><topic>Male</topic><topic>mechanism of action</topic><topic>Medical sciences</topic><topic>medicinal plants</topic><topic>Mice</topic><topic>Muscle, Smooth, Vascular - drug effects</topic><topic>Muscle, Smooth, Vascular - metabolism</topic><topic>Muscle, Smooth, Vascular - pathology</topic><topic>Neointima - prevention & control</topic><topic>neointima formation</topic><topic>Neointimal hyperplasia</topic><topic>oral administration</topic><topic>Pharmacognosy. Homeopathy. Health food</topic><topic>Pharmacology. Drug treatments</topic><topic>Phytotherapy</topic><topic>plant extracts</topic><topic>Plant Extracts - pharmacology</topic><topic>Plants, Medicinal</topic><topic>Plaque, Atherosclerotic - pathology</topic><topic>Plaque, Atherosclerotic - prevention & control</topic><topic>Platelet-Derived Growth Factor - metabolism</topic><topic>Proto-Oncogene Proteins c-sis</topic><topic>Rats</topic><topic>Restenosis</topic><topic>Signal Transduction</topic><topic>smooth muscle</topic><topic>stenosis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Jo Woon Yi</creatorcontrib><creatorcontrib>Lee, Bok-Soo</creatorcontrib><creatorcontrib>Lee, Ji Yeun</creatorcontrib><creatorcontrib>Ku, Hyo Jung</creatorcontrib><creatorcontrib>Jeon, So-Ra</creatorcontrib><creatorcontrib>Kim, Joo Yun</creatorcontrib><creatorcontrib>Ban, Ji Min</creatorcontrib><creatorcontrib>Sung, Sang Hyun</creatorcontrib><creatorcontrib>Shin, Heung Mook</creatorcontrib><creatorcontrib>Park, Jeong Euy</creatorcontrib><collection>AGRIS</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 ethnopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Jo Woon Yi</au><au>Lee, Bok-Soo</au><au>Lee, Ji Yeun</au><au>Ku, Hyo Jung</au><au>Jeon, So-Ra</au><au>Kim, Joo Yun</au><au>Ban, Ji Min</au><au>Sung, Sang Hyun</au><au>Shin, Heung Mook</au><au>Park, Jeong Euy</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The herbal extract HMC05 inhibits neointima formation in balloon-injured rat carotid arteries: Possible therapeutic implications of HMC05</atitle><jtitle>Journal of ethnopharmacology</jtitle><addtitle>J Ethnopharmacol</addtitle><date>2011-01-07</date><risdate>2011</risdate><volume>133</volume><issue>1</issue><spage>168</spage><epage>176</epage><pages>168-176</pages><issn>0378-8741</issn><eissn>1872-7573</eissn><coden>JOETD7</coden><abstract>In a previous study, HMC05, a water extract from eight medicinal herbs was demonstrated to possess anti-inflammatory effects in murine macrophages and anti-atherosclerotic effects in apoE
−/− mice. HSP27 expression was shown to be decreased in advanced atherosclerotic plaques of human carotid arteries. In the present study, the role of HMC05 in the prevention of restenosis and the possible mechanisms involved in the decrease of neointima formation were investigated using
in vivo balloon injury rat model and
in vitro biochemical assays.
A rat carotid artery balloon injury restenosis model was used. Different doses of HMC05 were administered to the rats by tube feeding, starting from four days before surgery and continuing twice per week for two weeks after carotid injury. Injured carotid arteries isolated from rats were embedded in paraffin block and tissue sections were stained with H&E to assess neointima formation. Mechanism by HMC05 that are involved in smooth muscle cell proliferation and migration was assessed by western blot assay, immunohistochemistry and confocal analysis.
There was no significant difference in the medial area between the control and HMC05-treated groups. However, neointima formation was significantly inhibited in the HMC05-treated group, resulting in 47-fold lower intima to media ratios in rats treated with 25
mg/kg/day HMC05 as compared to the control. Surprisingly, monocytes infiltration in the neointima area was almost completely blocked by HMC05 administration. When rat vascular SMCs were treated with HMC05, the proliferation and migration of smooth muscle cells was dramatically inhibited in a dye uptake assay and in a scratch model in a culture dish, respectively. HMC05 dose-dependently inhibited PDGF-mediated MAPK and AKT activation. However, HMC05 did not affect PDGF-mediated HSP27 phosphorylation but it induced HSP27 overexpression and phosphorylation. In addition, medial SMCs in the arterial wall of rats treated with HMC05 showed a significant increase in HSP27 expression compared with that of the control rats.
HMC05, a strong anti-inflammatory reagent, might use HSP27 as an effector molecule in SMCs to reduce neointimal hyperplasia by inhibiting PDGF-mediated MAPK and AKT activation. HMC05 could be a useful drug candidate for the prevention of restenosis after balloon injury of the arteries.</abstract><cop>Shannon</cop><pub>Elsevier Ireland Ltd</pub><pmid>20883768</pmid><doi>10.1016/j.jep.2010.09.015</doi><tpages>9</tpages></addata></record> |
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subjects | animal models animal tissues Animals Anti-Inflammatory Agents - pharmacology arterial intima atherosclerosis Balloon injury model biochemical pathways Biological and medical sciences blood flow carotid arteries Carotid Arteries - drug effects Carotid Arteries - metabolism Carotid Artery Injuries - pathology Catheterization cell migration Cell Movement - drug effects cell proliferation Cell Proliferation - drug effects Cells, Cultured Coronary Restenosis - prevention & control Disease Models, Animal dosage dose response drug formulations General pharmacology Herb herbal medicines histopathology HMC05 HSP27 Heat-Shock Proteins - metabolism Humans hyperplasia immunohistochemistry in vitro studies in vivo studies inflammation Male mechanism of action Medical sciences medicinal plants Mice Muscle, Smooth, Vascular - drug effects Muscle, Smooth, Vascular - metabolism Muscle, Smooth, Vascular - pathology Neointima - prevention & control neointima formation Neointimal hyperplasia oral administration Pharmacognosy. Homeopathy. Health food Pharmacology. Drug treatments Phytotherapy plant extracts Plant Extracts - pharmacology Plants, Medicinal Plaque, Atherosclerotic - pathology Plaque, Atherosclerotic - prevention & control Platelet-Derived Growth Factor - metabolism Proto-Oncogene Proteins c-sis Rats Restenosis Signal Transduction smooth muscle stenosis |
title | The herbal extract HMC05 inhibits neointima formation in balloon-injured rat carotid arteries: Possible therapeutic implications of HMC05 |
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