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Pravastatin and Sarpogrelate Synergistically Ameliorate Atherosclerosis in LDLr-Knockout Mice
Pravastatin is a lipid-lowering agent that attenuates atherosclerosis. However, the multifactorial pathogenesis of atherosclerosis requires other drugs with different anti-atherogenic mechanisms. We chose sarpogrelate as an anti-platelet agent and a novel component of a complex drug with pravastatin...
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| Published in: | PloS one 2016-03, Vol.11 (3), p.e0150791-e0150791 |
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| container_end_page | e0150791 |
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| creator | Park, Kyung-Yeon Oh, Euichaul Kwak, Mi-Kyoung Jun, Hyun Sik Heo, Tae-Hwe |
| description | Pravastatin is a lipid-lowering agent that attenuates atherosclerosis. However, the multifactorial pathogenesis of atherosclerosis requires other drugs with different anti-atherogenic mechanisms. We chose sarpogrelate as an anti-platelet agent and a novel component of a complex drug with pravastatin due to its high potential but little information on its beneficial effects on atherosclerosis. Low-density lipoprotein receptor-knockout mice were fed a high-fat, high-cholesterol diet and treated with pravastatin alone, sarpogrelate alone, or a combination of both drugs. Although sarpogrelate alone did not significantly reduce atherosclerotic plaque areas, co-treatment with pravastatin significantly decreased aortic lesions compared to those of the pravastatin alone treated group. The combined therapy was markedly more effective than that of the single therapies in terms of foam cell formation, smooth muscle cell proliferation, and inflammatory cytokine levels. These results suggest that pravastatin and sarpogrelate combined therapy may provide a new therapeutic strategy for treating atherosclerosis. |
| doi_str_mv | 10.1371/journal.pone.0150791 |
| format | article |
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However, the multifactorial pathogenesis of atherosclerosis requires other drugs with different anti-atherogenic mechanisms. We chose sarpogrelate as an anti-platelet agent and a novel component of a complex drug with pravastatin due to its high potential but little information on its beneficial effects on atherosclerosis. Low-density lipoprotein receptor-knockout mice were fed a high-fat, high-cholesterol diet and treated with pravastatin alone, sarpogrelate alone, or a combination of both drugs. Although sarpogrelate alone did not significantly reduce atherosclerotic plaque areas, co-treatment with pravastatin significantly decreased aortic lesions compared to those of the pravastatin alone treated group. The combined therapy was markedly more effective than that of the single therapies in terms of foam cell formation, smooth muscle cell proliferation, and inflammatory cytokine levels. These results suggest that pravastatin and sarpogrelate combined therapy may provide a new therapeutic strategy for treating atherosclerosis.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0150791</identifier><identifier>PMID: 26950217</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Aorta ; Arteriosclerosis ; Atherosclerosis ; Atherosclerosis - blood ; Atherosclerosis - drug therapy ; Atherosclerosis - genetics ; Atherosclerosis - immunology ; Biology and Life Sciences ; Blood platelets ; Cardiovascular disease ; Cell proliferation ; Cell Proliferation - drug effects ; Cholesterol ; Comparative analysis ; Complications and side effects ; Coronary vessels ; Cytokines - metabolism ; Diabetes ; Diet ; Dosage and administration ; Drug Synergism ; Drug therapy ; Drugs ; Foam ; Foams ; Gene Expression Regulation - drug effects ; Gene Knockout Techniques ; Genetic aspects ; Heart attacks ; Histology ; Hypolipidemic Agents - pharmacology ; Hypolipidemic Agents - therapeutic use ; Inflammation ; Intercellular Adhesion Molecule-1 - metabolism ; Laboratory animals ; Lesions ; Lipids - blood ; Lipoprotein (low density) receptors ; Low density lipoprotein receptors ; Low density lipoproteins ; Macrophages - drug effects ; Macrophages - immunology ; Male ; Medicine and Health Sciences ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Monocytes - drug effects ; Monocytes - immunology ; Muscles ; Myocytes, Smooth Muscle - drug effects ; Myocytes, Smooth Muscle - pathology ; Pathogenesis ; Pharmaceutical sciences ; Pharmacy ; Physiological aspects ; Plaque, Atherosclerotic - prevention & control ; Pravastatin ; Pravastatin - pharmacology ; Pravastatin - therapeutic use ; Rabbits ; Receptor density ; Receptors, LDL - deficiency ; Receptors, LDL - genetics ; Rodents ; Signal transduction ; Smooth muscle ; Statins ; Studies ; Succinates - pharmacology ; Succinates - therapeutic use ; Therapy ; Thrombosis ; Transgenic animals</subject><ispartof>PloS one, 2016-03, Vol.11 (3), p.e0150791-e0150791</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Park et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2016 Park et al 2016 Park et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-81e9caa09bf157f83ba513fd85cd0c9321b76891ef436deffcd4fb4bf3c80f903</citedby><cites>FETCH-LOGICAL-c692t-81e9caa09bf157f83ba513fd85cd0c9321b76891ef436deffcd4fb4bf3c80f903</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1771230316/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1771230316?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26950217$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Chung, Yeonseok</contributor><creatorcontrib>Park, Kyung-Yeon</creatorcontrib><creatorcontrib>Oh, Euichaul</creatorcontrib><creatorcontrib>Kwak, Mi-Kyoung</creatorcontrib><creatorcontrib>Jun, Hyun Sik</creatorcontrib><creatorcontrib>Heo, Tae-Hwe</creatorcontrib><title>Pravastatin and Sarpogrelate Synergistically Ameliorate Atherosclerosis in LDLr-Knockout Mice</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Pravastatin is a lipid-lowering agent that attenuates atherosclerosis. However, the multifactorial pathogenesis of atherosclerosis requires other drugs with different anti-atherogenic mechanisms. We chose sarpogrelate as an anti-platelet agent and a novel component of a complex drug with pravastatin due to its high potential but little information on its beneficial effects on atherosclerosis. Low-density lipoprotein receptor-knockout mice were fed a high-fat, high-cholesterol diet and treated with pravastatin alone, sarpogrelate alone, or a combination of both drugs. Although sarpogrelate alone did not significantly reduce atherosclerotic plaque areas, co-treatment with pravastatin significantly decreased aortic lesions compared to those of the pravastatin alone treated group. The combined therapy was markedly more effective than that of the single therapies in terms of foam cell formation, smooth muscle cell proliferation, and inflammatory cytokine levels. These results suggest that pravastatin and sarpogrelate combined therapy may provide a new therapeutic strategy for treating atherosclerosis.</description><subject>Animals</subject><subject>Aorta</subject><subject>Arteriosclerosis</subject><subject>Atherosclerosis</subject><subject>Atherosclerosis - blood</subject><subject>Atherosclerosis - drug therapy</subject><subject>Atherosclerosis - genetics</subject><subject>Atherosclerosis - immunology</subject><subject>Biology and Life Sciences</subject><subject>Blood platelets</subject><subject>Cardiovascular disease</subject><subject>Cell proliferation</subject><subject>Cell Proliferation - drug effects</subject><subject>Cholesterol</subject><subject>Comparative analysis</subject><subject>Complications and side effects</subject><subject>Coronary vessels</subject><subject>Cytokines - metabolism</subject><subject>Diabetes</subject><subject>Diet</subject><subject>Dosage and administration</subject><subject>Drug Synergism</subject><subject>Drug therapy</subject><subject>Drugs</subject><subject>Foam</subject><subject>Foams</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Gene Knockout Techniques</subject><subject>Genetic aspects</subject><subject>Heart attacks</subject><subject>Histology</subject><subject>Hypolipidemic Agents - pharmacology</subject><subject>Hypolipidemic Agents - therapeutic use</subject><subject>Inflammation</subject><subject>Intercellular Adhesion Molecule-1 - metabolism</subject><subject>Laboratory animals</subject><subject>Lesions</subject><subject>Lipids - blood</subject><subject>Lipoprotein (low density) receptors</subject><subject>Low density lipoprotein receptors</subject><subject>Low density lipoproteins</subject><subject>Macrophages - drug effects</subject><subject>Macrophages - immunology</subject><subject>Male</subject><subject>Medicine and Health Sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Monocytes - drug effects</subject><subject>Monocytes - immunology</subject><subject>Muscles</subject><subject>Myocytes, Smooth Muscle - drug effects</subject><subject>Myocytes, Smooth Muscle - pathology</subject><subject>Pathogenesis</subject><subject>Pharmaceutical sciences</subject><subject>Pharmacy</subject><subject>Physiological aspects</subject><subject>Plaque, Atherosclerotic - prevention & control</subject><subject>Pravastatin</subject><subject>Pravastatin - pharmacology</subject><subject>Pravastatin - therapeutic use</subject><subject>Rabbits</subject><subject>Receptor density</subject><subject>Receptors, LDL - deficiency</subject><subject>Receptors, LDL - genetics</subject><subject>Rodents</subject><subject>Signal transduction</subject><subject>Smooth muscle</subject><subject>Statins</subject><subject>Studies</subject><subject>Succinates - pharmacology</subject><subject>Succinates - therapeutic use</subject><subject>Therapy</subject><subject>Thrombosis</subject><subject>Transgenic animals</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNqNk9Fu0zAUhiMEYmPwBggiISF20WLHTuLcIFUDRkXREAXukHXi2KmLGxfbmejb49JsatAuUCTHsr__t8_xOUnyFKMpJiV-vba968BMt7aTU4RzVFb4XnKKK5JNigyR-0fzk-SR92uEcsKK4mFykhVVjjJcniY_Pju4Bh8g6C6FrkmX4La2ddJAkOly10nXah-0AGN26WwjjbZuvzULK-msF2Y_ap9G-eLtwk0-dlb8tH1IP2khHycPFBgvnwz_s-Tb-3dfLz5MFleX84vZYiKKKgsThmUlAFBVK5yXipEackxUw3LRIBGDwHVZsApLRUnRSKVEQ1VNa0UEQ6pC5Cx5fvDdGuv5kBnPcVnijCCCi0jMD0RjYc23Tm_A7bgFzf8uWNdycDFMI7miDa7jDVhdM5qXBCpR4VxhAFwhysro9WY4ra83shGyCw7MyHS80-kVb-01pyVDLGPR4NVg4OyvXvrAN9oLaQx00vaHe5cZZZhG9MU_6N3RDVQLMQDdKRvPFXtTPqM0p0VGaB6p6R1U_Bq50SKWkdJxfSQ4HwkiE-Tv0ELvPZ8vv_w_e_V9zL48YlcSTFh5a_qgbefHID2AIhaZd1LdJhkjvu-Cm2zwfRfwoQui7NnxA92Kbsqe_AEUqwMx</recordid><startdate>20160307</startdate><enddate>20160307</enddate><creator>Park, Kyung-Yeon</creator><creator>Oh, Euichaul</creator><creator>Kwak, Mi-Kyoung</creator><creator>Jun, Hyun Sik</creator><creator>Heo, Tae-Hwe</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20160307</creationdate><title>Pravastatin and Sarpogrelate Synergistically Ameliorate Atherosclerosis in LDLr-Knockout Mice</title><author>Park, Kyung-Yeon ; Oh, Euichaul ; Kwak, Mi-Kyoung ; Jun, Hyun Sik ; Heo, Tae-Hwe</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-81e9caa09bf157f83ba513fd85cd0c9321b76891ef436deffcd4fb4bf3c80f903</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Aorta</topic><topic>Arteriosclerosis</topic><topic>Atherosclerosis</topic><topic>Atherosclerosis - blood</topic><topic>Atherosclerosis - drug therapy</topic><topic>Atherosclerosis - genetics</topic><topic>Atherosclerosis - immunology</topic><topic>Biology and Life Sciences</topic><topic>Blood platelets</topic><topic>Cardiovascular disease</topic><topic>Cell proliferation</topic><topic>Cell Proliferation - drug effects</topic><topic>Cholesterol</topic><topic>Comparative analysis</topic><topic>Complications and side effects</topic><topic>Coronary vessels</topic><topic>Cytokines - metabolism</topic><topic>Diabetes</topic><topic>Diet</topic><topic>Dosage and administration</topic><topic>Drug Synergism</topic><topic>Drug therapy</topic><topic>Drugs</topic><topic>Foam</topic><topic>Foams</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Gene Knockout Techniques</topic><topic>Genetic aspects</topic><topic>Heart attacks</topic><topic>Histology</topic><topic>Hypolipidemic Agents - pharmacology</topic><topic>Hypolipidemic Agents - therapeutic use</topic><topic>Inflammation</topic><topic>Intercellular Adhesion Molecule-1 - metabolism</topic><topic>Laboratory animals</topic><topic>Lesions</topic><topic>Lipids - blood</topic><topic>Lipoprotein (low density) receptors</topic><topic>Low density lipoprotein receptors</topic><topic>Low density lipoproteins</topic><topic>Macrophages - drug effects</topic><topic>Macrophages - immunology</topic><topic>Male</topic><topic>Medicine and Health Sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Monocytes - drug effects</topic><topic>Monocytes - immunology</topic><topic>Muscles</topic><topic>Myocytes, Smooth Muscle - drug effects</topic><topic>Myocytes, Smooth Muscle - pathology</topic><topic>Pathogenesis</topic><topic>Pharmaceutical sciences</topic><topic>Pharmacy</topic><topic>Physiological aspects</topic><topic>Plaque, Atherosclerotic - prevention & control</topic><topic>Pravastatin</topic><topic>Pravastatin - pharmacology</topic><topic>Pravastatin - therapeutic use</topic><topic>Rabbits</topic><topic>Receptor density</topic><topic>Receptors, LDL - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals (Open Access)</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Park, Kyung-Yeon</au><au>Oh, Euichaul</au><au>Kwak, Mi-Kyoung</au><au>Jun, Hyun Sik</au><au>Heo, Tae-Hwe</au><au>Chung, Yeonseok</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pravastatin and Sarpogrelate Synergistically Ameliorate Atherosclerosis in LDLr-Knockout Mice</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-03-07</date><risdate>2016</risdate><volume>11</volume><issue>3</issue><spage>e0150791</spage><epage>e0150791</epage><pages>e0150791-e0150791</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Pravastatin is a lipid-lowering agent that attenuates atherosclerosis. However, the multifactorial pathogenesis of atherosclerosis requires other drugs with different anti-atherogenic mechanisms. We chose sarpogrelate as an anti-platelet agent and a novel component of a complex drug with pravastatin due to its high potential but little information on its beneficial effects on atherosclerosis. Low-density lipoprotein receptor-knockout mice were fed a high-fat, high-cholesterol diet and treated with pravastatin alone, sarpogrelate alone, or a combination of both drugs. Although sarpogrelate alone did not significantly reduce atherosclerotic plaque areas, co-treatment with pravastatin significantly decreased aortic lesions compared to those of the pravastatin alone treated group. The combined therapy was markedly more effective than that of the single therapies in terms of foam cell formation, smooth muscle cell proliferation, and inflammatory cytokine levels. These results suggest that pravastatin and sarpogrelate combined therapy may provide a new therapeutic strategy for treating atherosclerosis.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26950217</pmid><doi>10.1371/journal.pone.0150791</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2016-03, Vol.11 (3), p.e0150791-e0150791 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1771230316 |
| source | PubMed Central (Open Access); Publicly Available Content (ProQuest) |
| subjects | Animals Aorta Arteriosclerosis Atherosclerosis Atherosclerosis - blood Atherosclerosis - drug therapy Atherosclerosis - genetics Atherosclerosis - immunology Biology and Life Sciences Blood platelets Cardiovascular disease Cell proliferation Cell Proliferation - drug effects Cholesterol Comparative analysis Complications and side effects Coronary vessels Cytokines - metabolism Diabetes Diet Dosage and administration Drug Synergism Drug therapy Drugs Foam Foams Gene Expression Regulation - drug effects Gene Knockout Techniques Genetic aspects Heart attacks Histology Hypolipidemic Agents - pharmacology Hypolipidemic Agents - therapeutic use Inflammation Intercellular Adhesion Molecule-1 - metabolism Laboratory animals Lesions Lipids - blood Lipoprotein (low density) receptors Low density lipoprotein receptors Low density lipoproteins Macrophages - drug effects Macrophages - immunology Male Medicine and Health Sciences Mice Mice, Inbred C57BL Mice, Knockout Monocytes - drug effects Monocytes - immunology Muscles Myocytes, Smooth Muscle - drug effects Myocytes, Smooth Muscle - pathology Pathogenesis Pharmaceutical sciences Pharmacy Physiological aspects Plaque, Atherosclerotic - prevention & control Pravastatin Pravastatin - pharmacology Pravastatin - therapeutic use Rabbits Receptor density Receptors, LDL - deficiency Receptors, LDL - genetics Rodents Signal transduction Smooth muscle Statins Studies Succinates - pharmacology Succinates - therapeutic use Therapy Thrombosis Transgenic animals |
| title | Pravastatin and Sarpogrelate Synergistically Ameliorate Atherosclerosis in LDLr-Knockout Mice |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-27T06%3A29%3A52IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Pravastatin%20and%20Sarpogrelate%20Synergistically%20Ameliorate%20Atherosclerosis%20in%20LDLr-Knockout%20Mice&rft.jtitle=PloS%20one&rft.au=Park,%20Kyung-Yeon&rft.date=2016-03-07&rft.volume=11&rft.issue=3&rft.spage=e0150791&rft.epage=e0150791&rft.pages=e0150791-e0150791&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0150791&rft_dat=%3Cgale_plos_%3EA445462345%3C/gale_plos_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c692t-81e9caa09bf157f83ba513fd85cd0c9321b76891ef436deffcd4fb4bf3c80f903%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1771230316&rft_id=info:pmid/26950217&rft_galeid=A445462345&rfr_iscdi=true |