DNA hypomethylation and methyltransferase expression in atherosclerotic lesions
Arterial smooth muscle cell (SMC) migration and proliferation are central features in atherogenesis. Altered gene expression and cell proliferation in atherosclerotic lesions have some similar characteristics with certain solid tumors and thus might have similar mechanisms that lead to SMC prolifera...
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creator | Hiltunen, Mikko O Turunen, Mikko P Häkkinen, Tomi P Rutanen, Juha Hedman, Marja Mäkinen, Kimmo Turunen, Anna-Mari Aalto-Setalä, Katriina Ylä-Herttuala, Seppo |
description | Arterial smooth muscle cell (SMC) migration and proliferation are central features in atherogenesis. Altered gene expression and cell proliferation in atherosclerotic lesions have some similar characteristics with certain solid tumors and thus might have similar mechanisms that lead to SMC proliferation. Among cancer cells common features are genome-wide hypomethylation which correlates with transformation and tumor progression, and coincident over-expression of methyltransferase (MTase). The purpose of the present study was to analyze whether alterations in DNA methylation and MTase expression are present in atherosclerotic lesions.
A significant reduction in genomic 5-methylcytosine content was detected in advanced human atherosclerotic lesions and in lesions of ApoE knock-out mice. SMC were shown to develop hypomethylation in vitro during transformation from a contractile to synthetic pheno-type. Balloon denudation of New Zealand White rabbit aorta caused proliferation of intimal SMC with concomitant genomic hypomethylation in the thickened intima. By using in situ hybridization the overall transcriptional activity was found to be increased in clusters of lesion SMC. Marked heterogeneity was seen in MTase mRNA expression in various types of atherosclerotic lesions among intimal and medial SMC.
These findings show that (1) genomic hypomethylation occurs during atherogenesis in human, mouse and rabbit lesions and that it correlates with increased transcriptional activity; (2) MTase is expressed in atherosclerotic lesions; and (3) hypomethylation is present in advanced lesions at the same level as in malignant tumors and may affect cellular proliferation and gene expression in atherosclerotic lesions. |
doi_str_mv | 10.1191/1358863x02vm418oa |
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A significant reduction in genomic 5-methylcytosine content was detected in advanced human atherosclerotic lesions and in lesions of ApoE knock-out mice. SMC were shown to develop hypomethylation in vitro during transformation from a contractile to synthetic pheno-type. Balloon denudation of New Zealand White rabbit aorta caused proliferation of intimal SMC with concomitant genomic hypomethylation in the thickened intima. By using in situ hybridization the overall transcriptional activity was found to be increased in clusters of lesion SMC. Marked heterogeneity was seen in MTase mRNA expression in various types of atherosclerotic lesions among intimal and medial SMC.
These findings show that (1) genomic hypomethylation occurs during atherogenesis in human, mouse and rabbit lesions and that it correlates with increased transcriptional activity; (2) MTase is expressed in atherosclerotic lesions; and (3) hypomethylation is present in advanced lesions at the same level as in malignant tumors and may affect cellular proliferation and gene expression in atherosclerotic lesions.</description><identifier>ISSN: 1358-836X</identifier><identifier>ISSN: 1358-863X</identifier><identifier>EISSN: 1477-0377</identifier><identifier>DOI: 10.1191/1358863x02vm418oa</identifier><identifier>PMID: 12083735</identifier><language>eng</language><publisher>Thousand Oaks, CA: Sage Publications</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Animals ; Aorta - metabolism ; Aorta - pathology ; Arteriosclerosis - genetics ; Arteriosclerosis - metabolism ; Atherosclerosis (general aspects, experimental research) ; Biological and medical sciences ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Cell Movement - genetics ; Child ; Disease Models, Animal ; DNA - genetics ; DNA - metabolism ; DNA Methylation ; DNA Modification Methylases - biosynthesis ; DNA Modification Methylases - genetics ; Female ; Gene Expression - genetics ; Humans ; Male ; Medical sciences ; Mice ; Mice, Knockout ; Middle Aged ; Models, Cardiovascular ; Myocytes, Smooth Muscle - metabolism ; Proto-Oncogene Proteins c-sis - biosynthesis ; Proto-Oncogene Proteins c-sis - genetics ; Rabbits ; RNA, Messenger - biosynthesis ; RNA, Messenger - genetics ; Tunica Intima - metabolism</subject><ispartof>Vascular medicine (London, England), 2002-02, Vol.7 (1), p.5-11</ispartof><rights>2002 INIST-CNRS</rights><rights>2002 Arnold</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c491t-3ceccdea888d5f6b3ffd5fef1588684da197e5c0255f2593140f92a9e1d9ace3</citedby><cites>FETCH-LOGICAL-c491t-3ceccdea888d5f6b3ffd5fef1588684da197e5c0255f2593140f92a9e1d9ace3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1191/1358863x02vm418oa$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1191/1358863x02vm418oa$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>314,780,784,21819,27924,27925,43621,43622</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13673274$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12083735$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hiltunen, Mikko O</creatorcontrib><creatorcontrib>Turunen, Mikko P</creatorcontrib><creatorcontrib>Häkkinen, Tomi P</creatorcontrib><creatorcontrib>Rutanen, Juha</creatorcontrib><creatorcontrib>Hedman, Marja</creatorcontrib><creatorcontrib>Mäkinen, Kimmo</creatorcontrib><creatorcontrib>Turunen, Anna-Mari</creatorcontrib><creatorcontrib>Aalto-Setalä, Katriina</creatorcontrib><creatorcontrib>Ylä-Herttuala, Seppo</creatorcontrib><title>DNA hypomethylation and methyltransferase expression in atherosclerotic lesions</title><title>Vascular medicine (London, England)</title><addtitle>Vasc Med</addtitle><description>Arterial smooth muscle cell (SMC) migration and proliferation are central features in atherogenesis. Altered gene expression and cell proliferation in atherosclerotic lesions have some similar characteristics with certain solid tumors and thus might have similar mechanisms that lead to SMC proliferation. Among cancer cells common features are genome-wide hypomethylation which correlates with transformation and tumor progression, and coincident over-expression of methyltransferase (MTase). The purpose of the present study was to analyze whether alterations in DNA methylation and MTase expression are present in atherosclerotic lesions.
A significant reduction in genomic 5-methylcytosine content was detected in advanced human atherosclerotic lesions and in lesions of ApoE knock-out mice. SMC were shown to develop hypomethylation in vitro during transformation from a contractile to synthetic pheno-type. Balloon denudation of New Zealand White rabbit aorta caused proliferation of intimal SMC with concomitant genomic hypomethylation in the thickened intima. By using in situ hybridization the overall transcriptional activity was found to be increased in clusters of lesion SMC. Marked heterogeneity was seen in MTase mRNA expression in various types of atherosclerotic lesions among intimal and medial SMC.
These findings show that (1) genomic hypomethylation occurs during atherogenesis in human, mouse and rabbit lesions and that it correlates with increased transcriptional activity; (2) MTase is expressed in atherosclerotic lesions; and (3) hypomethylation is present in advanced lesions at the same level as in malignant tumors and may affect cellular proliferation and gene expression in atherosclerotic lesions.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Animals</subject><subject>Aorta - metabolism</subject><subject>Aorta - pathology</subject><subject>Arteriosclerosis - genetics</subject><subject>Arteriosclerosis - metabolism</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 Movement - genetics</subject><subject>Child</subject><subject>Disease Models, Animal</subject><subject>DNA - genetics</subject><subject>DNA - metabolism</subject><subject>DNA Methylation</subject><subject>DNA Modification Methylases - biosynthesis</subject><subject>DNA Modification Methylases - genetics</subject><subject>Female</subject><subject>Gene Expression - genetics</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Middle Aged</subject><subject>Models, Cardiovascular</subject><subject>Myocytes, Smooth Muscle - metabolism</subject><subject>Proto-Oncogene Proteins c-sis - biosynthesis</subject><subject>Proto-Oncogene Proteins c-sis - genetics</subject><subject>Rabbits</subject><subject>RNA, Messenger - biosynthesis</subject><subject>RNA, Messenger - genetics</subject><subject>Tunica Intima - metabolism</subject><issn>1358-836X</issn><issn>1358-863X</issn><issn>1477-0377</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp1kEtLAzEQx4MotlY_gBdZBL1tzWw2m-RY6hOKvfTgbUmzE7tlHzXZSvvtTWmhoHiZB_Ob15-Qa6BDAAUPwLiUGdvQ5LtOQbb6hPQhFSKmTIjTEId6LFn20SMX3i8ppSJTcE56kFDJBON9Mn18H0WL7aqtsVtsK92VbRPppoj2eed04y067THCzcqh9zugDEy3QNd6UwXblSaqcFfxl-TM6srj1cEPyOz5aTZ-jSfTl7fxaBKbVEEXM4PGFKillAW32ZxZGzxa2D0k00KDEsgNTTi3CVcMUmpVohVCobRBNiD3-7Er136t0Xd5XXqDVaUbbNc-FyA5ZCADePsLXLZr14TT8iRhgguV8gDBHjLhI-_Q5itX1tptc6D5Tun8j9Kh5-YweD2vsTh2HKQNwN0B0N7oygYlTemPHMsES0QauOGe8_oTj9f9v_kHwwyXpQ</recordid><startdate>200202</startdate><enddate>200202</enddate><creator>Hiltunen, Mikko O</creator><creator>Turunen, Mikko P</creator><creator>Häkkinen, Tomi P</creator><creator>Rutanen, Juha</creator><creator>Hedman, Marja</creator><creator>Mäkinen, Kimmo</creator><creator>Turunen, Anna-Mari</creator><creator>Aalto-Setalä, Katriina</creator><creator>Ylä-Herttuala, Seppo</creator><general>Sage Publications</general><general>Arnold</general><general>Sage Publications Ltd</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M7Z</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>200202</creationdate><title>DNA hypomethylation and methyltransferase expression in atherosclerotic lesions</title><author>Hiltunen, Mikko O ; Turunen, Mikko P ; Häkkinen, Tomi P ; Rutanen, Juha ; Hedman, Marja ; Mäkinen, Kimmo ; Turunen, Anna-Mari ; Aalto-Setalä, Katriina ; Ylä-Herttuala, Seppo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c491t-3ceccdea888d5f6b3ffd5fef1588684da197e5c0255f2593140f92a9e1d9ace3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Animals</topic><topic>Aorta - metabolism</topic><topic>Aorta - pathology</topic><topic>Arteriosclerosis - genetics</topic><topic>Arteriosclerosis - metabolism</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 Movement - genetics</topic><topic>Child</topic><topic>Disease Models, Animal</topic><topic>DNA - genetics</topic><topic>DNA - metabolism</topic><topic>DNA Methylation</topic><topic>DNA Modification Methylases - biosynthesis</topic><topic>DNA Modification Methylases - genetics</topic><topic>Female</topic><topic>Gene Expression - genetics</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Middle Aged</topic><topic>Models, Cardiovascular</topic><topic>Myocytes, Smooth Muscle - metabolism</topic><topic>Proto-Oncogene Proteins c-sis - biosynthesis</topic><topic>Proto-Oncogene Proteins c-sis - genetics</topic><topic>Rabbits</topic><topic>RNA, Messenger - biosynthesis</topic><topic>RNA, Messenger - genetics</topic><topic>Tunica Intima - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hiltunen, Mikko O</creatorcontrib><creatorcontrib>Turunen, Mikko P</creatorcontrib><creatorcontrib>Häkkinen, Tomi P</creatorcontrib><creatorcontrib>Rutanen, Juha</creatorcontrib><creatorcontrib>Hedman, Marja</creatorcontrib><creatorcontrib>Mäkinen, Kimmo</creatorcontrib><creatorcontrib>Turunen, Anna-Mari</creatorcontrib><creatorcontrib>Aalto-Setalä, Katriina</creatorcontrib><creatorcontrib>Ylä-Herttuala, Seppo</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>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biochemistry Abstracts 1</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Vascular medicine (London, England)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hiltunen, Mikko O</au><au>Turunen, Mikko P</au><au>Häkkinen, Tomi P</au><au>Rutanen, Juha</au><au>Hedman, Marja</au><au>Mäkinen, Kimmo</au><au>Turunen, Anna-Mari</au><au>Aalto-Setalä, Katriina</au><au>Ylä-Herttuala, Seppo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>DNA hypomethylation and methyltransferase expression in atherosclerotic lesions</atitle><jtitle>Vascular medicine (London, England)</jtitle><addtitle>Vasc Med</addtitle><date>2002-02</date><risdate>2002</risdate><volume>7</volume><issue>1</issue><spage>5</spage><epage>11</epage><pages>5-11</pages><issn>1358-836X</issn><issn>1358-863X</issn><eissn>1477-0377</eissn><abstract>Arterial smooth muscle cell (SMC) migration and proliferation are central features in atherogenesis. Altered gene expression and cell proliferation in atherosclerotic lesions have some similar characteristics with certain solid tumors and thus might have similar mechanisms that lead to SMC proliferation. Among cancer cells common features are genome-wide hypomethylation which correlates with transformation and tumor progression, and coincident over-expression of methyltransferase (MTase). The purpose of the present study was to analyze whether alterations in DNA methylation and MTase expression are present in atherosclerotic lesions.
A significant reduction in genomic 5-methylcytosine content was detected in advanced human atherosclerotic lesions and in lesions of ApoE knock-out mice. SMC were shown to develop hypomethylation in vitro during transformation from a contractile to synthetic pheno-type. Balloon denudation of New Zealand White rabbit aorta caused proliferation of intimal SMC with concomitant genomic hypomethylation in the thickened intima. By using in situ hybridization the overall transcriptional activity was found to be increased in clusters of lesion SMC. Marked heterogeneity was seen in MTase mRNA expression in various types of atherosclerotic lesions among intimal and medial SMC.
These findings show that (1) genomic hypomethylation occurs during atherogenesis in human, mouse and rabbit lesions and that it correlates with increased transcriptional activity; (2) MTase is expressed in atherosclerotic lesions; and (3) hypomethylation is present in advanced lesions at the same level as in malignant tumors and may affect cellular proliferation and gene expression in atherosclerotic lesions.</abstract><cop>Thousand Oaks, CA</cop><pub>Sage Publications</pub><pmid>12083735</pmid><doi>10.1191/1358863x02vm418oa</doi><tpages>7</tpages></addata></record> |
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subjects | Adolescent Adult Aged Aged, 80 and over Animals Aorta - metabolism Aorta - pathology Arteriosclerosis - genetics Arteriosclerosis - metabolism Atherosclerosis (general aspects, experimental research) Biological and medical sciences Blood and lymphatic vessels Cardiology. Vascular system Cell Movement - genetics Child Disease Models, Animal DNA - genetics DNA - metabolism DNA Methylation DNA Modification Methylases - biosynthesis DNA Modification Methylases - genetics Female Gene Expression - genetics Humans Male Medical sciences Mice Mice, Knockout Middle Aged Models, Cardiovascular Myocytes, Smooth Muscle - metabolism Proto-Oncogene Proteins c-sis - biosynthesis Proto-Oncogene Proteins c-sis - genetics Rabbits RNA, Messenger - biosynthesis RNA, Messenger - genetics Tunica Intima - metabolism |
title | DNA hypomethylation and methyltransferase expression in atherosclerotic lesions |
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