Alternation of histone and DNA methylation in human atherosclerotic carotid plaques
Summary Little is known about epigenetics and its possible role in atherosclerosis. We here analysed histone and DNA methylation and the expression of corresponding methyltransferases in early and advanced human atherosclerotic carotid lesions in comparison to healthy carotid arteries. Western Blott...
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| Veröffentlicht in: | Thrombosis and haemostasis 2015-08, Vol.113 (2), p.390-402 |
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| creator | Greißel, Anna Culmes, Mihaela Napieralski, Rudolf Wagner, Ernst Gebhard, Harry Schmitt, Manfred Zimmermann, Alexander Eckstein, Hans-Henning Zernecke, Alma Pelisek, Jaroslav |
| description | Summary
Little is known about epigenetics and its possible role in atherosclerosis. We here analysed histone and DNA methylation and the expression of corresponding methyltransferases in early and advanced human atherosclerotic carotid lesions in comparison to healthy carotid arteries. Western Blotting was performed on carotid plaques from our biobank with early (n=60) or advanced (n=60) stages of atherosclerosis and healthy carotid arteries (n=12) to analyse di-methylation patterns of histone H3 at positions K4, K9 and K27. In atherosclerotic lesions, di-methylation of H3K4 was unaltered and that of H3K9 and H3K27 significantly decreased compared to control arteries. Immunohistochemistry revealed an increased appearance of di-methylated H3K4 in smooth muscle cells (SMCs), a decreased expression of di-methylated H3K9 in SMCs and inflammatory cells, and reduced di-methylated H3K27 in inflammatory cells in advanced versus early atherosclerosis. Expression of corresponding histone methyltransferases MLL2 and G9a was increased in advanced versus early atherosclerosis. Genomic DNA hypomethylation, as determined by PCR for methylated LINE1 and SAT-alpha, was observed in early and advanced plaques compared to control arteries and in cell-free serum of patients with high-grade carotid stenosis compared to healthy volunteers. In contrast, no differences in DNA methylation were observed in blood cells. Expression of DNA-methyltransferase DNMT1 was reduced in atherosclerotic plaques versus controls, DNMT3A was undetectable, and DNMT3B not altered. DNA-demethylase TET1 was increased in atherosclerosisc plaques. The extent of histone and DNA methylation and expression of some corresponding methyltransferases are significantly altered in atherosclerosis, suggesting a possible contribution of epigenetics in disease development. |
| doi_str_mv | 10.1160/TH14-10-0852 |
| format | Article |
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Little is known about epigenetics and its possible role in atherosclerosis. We here analysed histone and DNA methylation and the expression of corresponding methyltransferases in early and advanced human atherosclerotic carotid lesions in comparison to healthy carotid arteries. Western Blotting was performed on carotid plaques from our biobank with early (n=60) or advanced (n=60) stages of atherosclerosis and healthy carotid arteries (n=12) to analyse di-methylation patterns of histone H3 at positions K4, K9 and K27. In atherosclerotic lesions, di-methylation of H3K4 was unaltered and that of H3K9 and H3K27 significantly decreased compared to control arteries. Immunohistochemistry revealed an increased appearance of di-methylated H3K4 in smooth muscle cells (SMCs), a decreased expression of di-methylated H3K9 in SMCs and inflammatory cells, and reduced di-methylated H3K27 in inflammatory cells in advanced versus early atherosclerosis. Expression of corresponding histone methyltransferases MLL2 and G9a was increased in advanced versus early atherosclerosis. Genomic DNA hypomethylation, as determined by PCR for methylated LINE1 and SAT-alpha, was observed in early and advanced plaques compared to control arteries and in cell-free serum of patients with high-grade carotid stenosis compared to healthy volunteers. In contrast, no differences in DNA methylation were observed in blood cells. Expression of DNA-methyltransferase DNMT1 was reduced in atherosclerotic plaques versus controls, DNMT3A was undetectable, and DNMT3B not altered. DNA-demethylase TET1 was increased in atherosclerosisc plaques. The extent of histone and DNA methylation and expression of some corresponding methyltransferases are significantly altered in atherosclerosis, suggesting a possible contribution of epigenetics in disease development.</description><identifier>ISSN: 0340-6245</identifier><identifier>EISSN: 2567-689X</identifier><identifier>DOI: 10.1160/TH14-10-0852</identifier><identifier>PMID: 25993995</identifier><language>eng</language><publisher>Germany: Schattauer GmbH</publisher><subject>Aged ; Blood Cells - metabolism ; Carotid Arteries - metabolism ; Carotid Artery Diseases - genetics ; Carotid Artery Diseases - metabolism ; Cellular Signalling and Proteolysis ; Disease Progression ; DNA (Cytosine-5-)-Methyltransferase 1 ; DNA (Cytosine-5-)-Methyltransferases - metabolism ; DNA Methylation ; DNA-Binding Proteins - metabolism ; Enzyme Induction ; Female ; Histocompatibility Antigens - metabolism ; Histone-Lysine N-Methyltransferase - metabolism ; Humans ; Inflammation ; Leukocytes - metabolism ; Long Interspersed Nucleotide Elements ; Lysine - metabolism ; Macrophages - metabolism ; Male ; Methylation ; Middle Aged ; Mixed Function Oxygenases ; Muscle, Smooth, Vascular - metabolism ; Muscle, Smooth, Vascular - pathology ; Myocytes, Smooth Muscle - metabolism ; Neoplasm Proteins - metabolism ; Plaque, Atherosclerotic - genetics ; Plaque, Atherosclerotic - metabolism ; Protein Processing, Post-Translational ; Proto-Oncogene Proteins - metabolism ; Real-Time Polymerase Chain Reaction</subject><ispartof>Thrombosis and haemostasis, 2015-08, Vol.113 (2), p.390-402</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c370t-64099f05e22b48cd7b5b954b85e6c7b9d07423cf6caad3c01e5e0fb6191e9d13</citedby><cites>FETCH-LOGICAL-c370t-64099f05e22b48cd7b5b954b85e6c7b9d07423cf6caad3c01e5e0fb6191e9d13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.thieme-connect.de/products/ejournals/pdf/10.1160/TH14-10-0852.pdf$$EPDF$$P50$$Gthieme$$H</linktopdf><linktohtml>$$Uhttps://www.thieme-connect.de/products/ejournals/html/10.1160/TH14-10-0852$$EHTML$$P50$$Gthieme$$H</linktohtml><link.rule.ids>314,778,782,3007,27907,27908,54542,54543</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25993995$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Greißel, Anna</creatorcontrib><creatorcontrib>Culmes, Mihaela</creatorcontrib><creatorcontrib>Napieralski, Rudolf</creatorcontrib><creatorcontrib>Wagner, Ernst</creatorcontrib><creatorcontrib>Gebhard, Harry</creatorcontrib><creatorcontrib>Schmitt, Manfred</creatorcontrib><creatorcontrib>Zimmermann, Alexander</creatorcontrib><creatorcontrib>Eckstein, Hans-Henning</creatorcontrib><creatorcontrib>Zernecke, Alma</creatorcontrib><creatorcontrib>Pelisek, Jaroslav</creatorcontrib><title>Alternation of histone and DNA methylation in human atherosclerotic carotid plaques</title><title>Thrombosis and haemostasis</title><addtitle>Thromb Haemost</addtitle><description>Summary
Little is known about epigenetics and its possible role in atherosclerosis. We here analysed histone and DNA methylation and the expression of corresponding methyltransferases in early and advanced human atherosclerotic carotid lesions in comparison to healthy carotid arteries. Western Blotting was performed on carotid plaques from our biobank with early (n=60) or advanced (n=60) stages of atherosclerosis and healthy carotid arteries (n=12) to analyse di-methylation patterns of histone H3 at positions K4, K9 and K27. In atherosclerotic lesions, di-methylation of H3K4 was unaltered and that of H3K9 and H3K27 significantly decreased compared to control arteries. Immunohistochemistry revealed an increased appearance of di-methylated H3K4 in smooth muscle cells (SMCs), a decreased expression of di-methylated H3K9 in SMCs and inflammatory cells, and reduced di-methylated H3K27 in inflammatory cells in advanced versus early atherosclerosis. Expression of corresponding histone methyltransferases MLL2 and G9a was increased in advanced versus early atherosclerosis. Genomic DNA hypomethylation, as determined by PCR for methylated LINE1 and SAT-alpha, was observed in early and advanced plaques compared to control arteries and in cell-free serum of patients with high-grade carotid stenosis compared to healthy volunteers. In contrast, no differences in DNA methylation were observed in blood cells. Expression of DNA-methyltransferase DNMT1 was reduced in atherosclerotic plaques versus controls, DNMT3A was undetectable, and DNMT3B not altered. DNA-demethylase TET1 was increased in atherosclerosisc plaques. The extent of histone and DNA methylation and expression of some corresponding methyltransferases are significantly altered in atherosclerosis, suggesting a possible contribution of epigenetics in disease development.</description><subject>Aged</subject><subject>Blood Cells - metabolism</subject><subject>Carotid Arteries - metabolism</subject><subject>Carotid Artery Diseases - genetics</subject><subject>Carotid Artery Diseases - metabolism</subject><subject>Cellular Signalling and Proteolysis</subject><subject>Disease Progression</subject><subject>DNA (Cytosine-5-)-Methyltransferase 1</subject><subject>DNA (Cytosine-5-)-Methyltransferases - metabolism</subject><subject>DNA Methylation</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Enzyme Induction</subject><subject>Female</subject><subject>Histocompatibility Antigens - metabolism</subject><subject>Histone-Lysine N-Methyltransferase - metabolism</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Leukocytes - metabolism</subject><subject>Long Interspersed Nucleotide Elements</subject><subject>Lysine - metabolism</subject><subject>Macrophages - metabolism</subject><subject>Male</subject><subject>Methylation</subject><subject>Middle Aged</subject><subject>Mixed Function Oxygenases</subject><subject>Muscle, Smooth, Vascular - metabolism</subject><subject>Muscle, Smooth, Vascular - pathology</subject><subject>Myocytes, Smooth Muscle - metabolism</subject><subject>Neoplasm Proteins - metabolism</subject><subject>Plaque, Atherosclerotic - genetics</subject><subject>Plaque, Atherosclerotic - metabolism</subject><subject>Protein Processing, Post-Translational</subject><subject>Proto-Oncogene Proteins - metabolism</subject><subject>Real-Time Polymerase Chain Reaction</subject><issn>0340-6245</issn><issn>2567-689X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkD1PwzAQhi0EoqWwMSPvYDgnthOPVfkoUgUDGdgix7koqfJRYmfovydRgInlXp3u0avTQ8g1h3vOFTwkWy4YBwaxDE7IMpAqYirWn6dkCaEApgIhF-TCuT0AV0LLc7IIpNah1nJJPta1x741vupa2hW0rJzvWqSmzenj25o26MtjPZ-rlpZDY1pqfIl952w9Tl9Zas2UOT3U5mtAd0nOClM7vPrJFUmen5LNlu3eX1436x2zYQSeKQFaFyAxCDIR2zzKZKalyGKJykaZziESQWgLZY3JQwscJUKRKa456pyHK3I319rxF9djkR76qjH9MeWQTmrSSc20TGpG_GbGD0PWYP4H_7oYgdsZ8GWFDab7bhjF1O7_um80Ym1b</recordid><startdate>20150801</startdate><enddate>20150801</enddate><creator>Greißel, Anna</creator><creator>Culmes, Mihaela</creator><creator>Napieralski, Rudolf</creator><creator>Wagner, Ernst</creator><creator>Gebhard, Harry</creator><creator>Schmitt, Manfred</creator><creator>Zimmermann, Alexander</creator><creator>Eckstein, Hans-Henning</creator><creator>Zernecke, Alma</creator><creator>Pelisek, Jaroslav</creator><general>Schattauer GmbH</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></search><sort><creationdate>20150801</creationdate><title>Alternation of histone and DNA methylation in human atherosclerotic carotid plaques</title><author>Greißel, Anna ; Culmes, Mihaela ; Napieralski, Rudolf ; Wagner, Ernst ; Gebhard, Harry ; Schmitt, Manfred ; Zimmermann, Alexander ; Eckstein, Hans-Henning ; Zernecke, Alma ; Pelisek, Jaroslav</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c370t-64099f05e22b48cd7b5b954b85e6c7b9d07423cf6caad3c01e5e0fb6191e9d13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Aged</topic><topic>Blood Cells - metabolism</topic><topic>Carotid Arteries - metabolism</topic><topic>Carotid Artery Diseases - genetics</topic><topic>Carotid Artery Diseases - metabolism</topic><topic>Cellular Signalling and Proteolysis</topic><topic>Disease Progression</topic><topic>DNA (Cytosine-5-)-Methyltransferase 1</topic><topic>DNA (Cytosine-5-)-Methyltransferases - metabolism</topic><topic>DNA Methylation</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Enzyme Induction</topic><topic>Female</topic><topic>Histocompatibility Antigens - metabolism</topic><topic>Histone-Lysine N-Methyltransferase - metabolism</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Leukocytes - metabolism</topic><topic>Long Interspersed Nucleotide Elements</topic><topic>Lysine - metabolism</topic><topic>Macrophages - metabolism</topic><topic>Male</topic><topic>Methylation</topic><topic>Middle Aged</topic><topic>Mixed Function Oxygenases</topic><topic>Muscle, Smooth, Vascular - metabolism</topic><topic>Muscle, Smooth, Vascular - pathology</topic><topic>Myocytes, Smooth Muscle - metabolism</topic><topic>Neoplasm Proteins - metabolism</topic><topic>Plaque, Atherosclerotic - genetics</topic><topic>Plaque, Atherosclerotic - metabolism</topic><topic>Protein Processing, Post-Translational</topic><topic>Proto-Oncogene Proteins - metabolism</topic><topic>Real-Time Polymerase Chain Reaction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Greißel, Anna</creatorcontrib><creatorcontrib>Culmes, Mihaela</creatorcontrib><creatorcontrib>Napieralski, Rudolf</creatorcontrib><creatorcontrib>Wagner, Ernst</creatorcontrib><creatorcontrib>Gebhard, Harry</creatorcontrib><creatorcontrib>Schmitt, Manfred</creatorcontrib><creatorcontrib>Zimmermann, Alexander</creatorcontrib><creatorcontrib>Eckstein, Hans-Henning</creatorcontrib><creatorcontrib>Zernecke, Alma</creatorcontrib><creatorcontrib>Pelisek, Jaroslav</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Thrombosis and haemostasis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Greißel, Anna</au><au>Culmes, Mihaela</au><au>Napieralski, Rudolf</au><au>Wagner, Ernst</au><au>Gebhard, Harry</au><au>Schmitt, Manfred</au><au>Zimmermann, Alexander</au><au>Eckstein, Hans-Henning</au><au>Zernecke, Alma</au><au>Pelisek, Jaroslav</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Alternation of histone and DNA methylation in human atherosclerotic carotid plaques</atitle><jtitle>Thrombosis and haemostasis</jtitle><addtitle>Thromb Haemost</addtitle><date>2015-08-01</date><risdate>2015</risdate><volume>113</volume><issue>2</issue><spage>390</spage><epage>402</epage><pages>390-402</pages><issn>0340-6245</issn><eissn>2567-689X</eissn><abstract>Summary
Little is known about epigenetics and its possible role in atherosclerosis. We here analysed histone and DNA methylation and the expression of corresponding methyltransferases in early and advanced human atherosclerotic carotid lesions in comparison to healthy carotid arteries. Western Blotting was performed on carotid plaques from our biobank with early (n=60) or advanced (n=60) stages of atherosclerosis and healthy carotid arteries (n=12) to analyse di-methylation patterns of histone H3 at positions K4, K9 and K27. In atherosclerotic lesions, di-methylation of H3K4 was unaltered and that of H3K9 and H3K27 significantly decreased compared to control arteries. Immunohistochemistry revealed an increased appearance of di-methylated H3K4 in smooth muscle cells (SMCs), a decreased expression of di-methylated H3K9 in SMCs and inflammatory cells, and reduced di-methylated H3K27 in inflammatory cells in advanced versus early atherosclerosis. Expression of corresponding histone methyltransferases MLL2 and G9a was increased in advanced versus early atherosclerosis. Genomic DNA hypomethylation, as determined by PCR for methylated LINE1 and SAT-alpha, was observed in early and advanced plaques compared to control arteries and in cell-free serum of patients with high-grade carotid stenosis compared to healthy volunteers. In contrast, no differences in DNA methylation were observed in blood cells. Expression of DNA-methyltransferase DNMT1 was reduced in atherosclerotic plaques versus controls, DNMT3A was undetectable, and DNMT3B not altered. DNA-demethylase TET1 was increased in atherosclerosisc plaques. The extent of histone and DNA methylation and expression of some corresponding methyltransferases are significantly altered in atherosclerosis, suggesting a possible contribution of epigenetics in disease development.</abstract><cop>Germany</cop><pub>Schattauer GmbH</pub><pmid>25993995</pmid><doi>10.1160/TH14-10-0852</doi><tpages>13</tpages></addata></record> |
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| subjects | Aged Blood Cells - metabolism Carotid Arteries - metabolism Carotid Artery Diseases - genetics Carotid Artery Diseases - metabolism Cellular Signalling and Proteolysis Disease Progression DNA (Cytosine-5-)-Methyltransferase 1 DNA (Cytosine-5-)-Methyltransferases - metabolism DNA Methylation DNA-Binding Proteins - metabolism Enzyme Induction Female Histocompatibility Antigens - metabolism Histone-Lysine N-Methyltransferase - metabolism Humans Inflammation Leukocytes - metabolism Long Interspersed Nucleotide Elements Lysine - metabolism Macrophages - metabolism Male Methylation Middle Aged Mixed Function Oxygenases Muscle, Smooth, Vascular - metabolism Muscle, Smooth, Vascular - pathology Myocytes, Smooth Muscle - metabolism Neoplasm Proteins - metabolism Plaque, Atherosclerotic - genetics Plaque, Atherosclerotic - metabolism Protein Processing, Post-Translational Proto-Oncogene Proteins - metabolism Real-Time Polymerase Chain Reaction |
| title | Alternation of histone and DNA methylation in human atherosclerotic carotid plaques |
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