Microarray Analysis Reveals Overexpression of CD163 and HO-1 in Symptomatic Carotid Plaques
OBJECTIVE—We studied by microarray analysis whether symptomatic and asymptomatic carotid plaques from the same patient differ in gene expression and whether the same changes are present in an independent sample set. METHODS AND RESULTS—Carotid plaques from four patients with bilateral high-grade ste...
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Veröffentlicht in: | Arteriosclerosis, thrombosis, and vascular biology thrombosis, and vascular biology, 2007-01, Vol.27 (1), p.154-160 |
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creator | Ijäs, Petra Nuotio, Krista Saksi, Jani Soinne, Lauri Saimanen, Eija Karjalainen-Lindsberg, Marja-Liisa Salonen, Oili Sarna, Seppo Tuimala, Jarno Kovanen, Petri T Kaste, Markku Lindsberg, Perttu J |
description | OBJECTIVE—We studied by microarray analysis whether symptomatic and asymptomatic carotid plaques from the same patient differ in gene expression and whether the same changes are present in an independent sample set.
METHODS AND RESULTS—Carotid plaques from four patients with bilateral high-grade stenosis, one being symptomatic and the other asymptomatic, were analyzed on Affymetrix U95Av2 arrays. 33 genes showed >1.5-fold change between symptomatic and asymptomatic plaques in an intraindividual comparison with FDR ranging from 0.28 to 0.40. Three genes involved in iron-heme homeostasis, CD163, HO-1, and transferrin receptor, were further analyzed in 40 independent plaques. HO-1 (fold-change 1.93, 95%CI 1.04 to 3.94, P=0.040) and CD163 (1.58, 1.11 to 2.40, P=0.013) mRNAs were again induced, and also HO-1 protein was overexpressed in symptomatic plaques (4.38, 1.54 to 12.20, P=0.024). The expression of HO-1 and CD163 correlated with tissue iron content but iron itself was not associated with the symptom status.
CONCLUSIONS—Symptomatic plaques show overexpression of CD163 and HO-1 both in intraindividual and interindividual comparison. Their expression correlates with iron deposits but asymptomatic and symptomatic plaques from isolated patients do not differ in macroscopic hemorrhages or iron deposits. We suggest that symptomatic plaques show a more pronounced induction of CD163 and HO-1 in response to plaque hemorrhages. |
doi_str_mv | 10.1161/01.ATV.0000251991.64617.e7 |
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METHODS AND RESULTS—Carotid plaques from four patients with bilateral high-grade stenosis, one being symptomatic and the other asymptomatic, were analyzed on Affymetrix U95Av2 arrays. 33 genes showed >1.5-fold change between symptomatic and asymptomatic plaques in an intraindividual comparison with FDR ranging from 0.28 to 0.40. Three genes involved in iron-heme homeostasis, CD163, HO-1, and transferrin receptor, were further analyzed in 40 independent plaques. HO-1 (fold-change 1.93, 95%CI 1.04 to 3.94, P=0.040) and CD163 (1.58, 1.11 to 2.40, P=0.013) mRNAs were again induced, and also HO-1 protein was overexpressed in symptomatic plaques (4.38, 1.54 to 12.20, P=0.024). The expression of HO-1 and CD163 correlated with tissue iron content but iron itself was not associated with the symptom status.
CONCLUSIONS—Symptomatic plaques show overexpression of CD163 and HO-1 both in intraindividual and interindividual comparison. Their expression correlates with iron deposits but asymptomatic and symptomatic plaques from isolated patients do not differ in macroscopic hemorrhages or iron deposits. We suggest that symptomatic plaques show a more pronounced induction of CD163 and HO-1 in response to plaque hemorrhages.</description><identifier>ISSN: 1079-5642</identifier><identifier>EISSN: 1524-4636</identifier><identifier>DOI: 10.1161/01.ATV.0000251991.64617.e7</identifier><identifier>PMID: 17095719</identifier><identifier>CODEN: ATVBFA</identifier><language>eng</language><publisher>Philadelphia, PA: American Heart Association, Inc</publisher><subject>Aged ; Antigens, CD - genetics ; Antigens, CD - metabolism ; Antigens, Differentiation, Myelomonocytic - genetics ; Antigens, Differentiation, Myelomonocytic - metabolism ; Atherosclerosis (general aspects, experimental research) ; Biological and medical sciences ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Carotid Stenosis - genetics ; Carotid Stenosis - metabolism ; Carotid Stenosis - physiopathology ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; DNA - genetics ; Female ; Gene Expression Regulation ; Heme - metabolism ; Heme Oxygenase-1 - genetics ; Heme Oxygenase-1 - metabolism ; Hemorrhage ; Humans ; Iron - metabolism ; Male ; Medical sciences ; Middle Aged ; Neurology ; Neurosurgery ; Oligonucleotide Array Sequence Analysis - methods ; Receptors, Cell Surface - genetics ; Receptors, Cell Surface - metabolism ; Receptors, Transferrin - genetics ; Receptors, Transferrin - metabolism ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Skull, brain, vascular surgery ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; Vascular diseases and vascular malformations of the nervous system</subject><ispartof>Arteriosclerosis, thrombosis, and vascular biology, 2007-01, Vol.27 (1), p.154-160</ispartof><rights>2007 American Heart Association, Inc.</rights><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4914-d7d0e464e9bc06e869305c8b78c309320800bde5e1e06c585ac9a6d7337044d03</citedby><cites>FETCH-LOGICAL-c4914-d7d0e464e9bc06e869305c8b78c309320800bde5e1e06c585ac9a6d7337044d03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,4010,27900,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18405024$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17095719$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ijäs, Petra</creatorcontrib><creatorcontrib>Nuotio, Krista</creatorcontrib><creatorcontrib>Saksi, Jani</creatorcontrib><creatorcontrib>Soinne, Lauri</creatorcontrib><creatorcontrib>Saimanen, Eija</creatorcontrib><creatorcontrib>Karjalainen-Lindsberg, Marja-Liisa</creatorcontrib><creatorcontrib>Salonen, Oili</creatorcontrib><creatorcontrib>Sarna, Seppo</creatorcontrib><creatorcontrib>Tuimala, Jarno</creatorcontrib><creatorcontrib>Kovanen, Petri T</creatorcontrib><creatorcontrib>Kaste, Markku</creatorcontrib><creatorcontrib>Lindsberg, Perttu J</creatorcontrib><title>Microarray Analysis Reveals Overexpression of CD163 and HO-1 in Symptomatic Carotid Plaques</title><title>Arteriosclerosis, thrombosis, and vascular biology</title><addtitle>Arterioscler Thromb Vasc Biol</addtitle><description>OBJECTIVE—We studied by microarray analysis whether symptomatic and asymptomatic carotid plaques from the same patient differ in gene expression and whether the same changes are present in an independent sample set.
METHODS AND RESULTS—Carotid plaques from four patients with bilateral high-grade stenosis, one being symptomatic and the other asymptomatic, were analyzed on Affymetrix U95Av2 arrays. 33 genes showed >1.5-fold change between symptomatic and asymptomatic plaques in an intraindividual comparison with FDR ranging from 0.28 to 0.40. Three genes involved in iron-heme homeostasis, CD163, HO-1, and transferrin receptor, were further analyzed in 40 independent plaques. HO-1 (fold-change 1.93, 95%CI 1.04 to 3.94, P=0.040) and CD163 (1.58, 1.11 to 2.40, P=0.013) mRNAs were again induced, and also HO-1 protein was overexpressed in symptomatic plaques (4.38, 1.54 to 12.20, P=0.024). The expression of HO-1 and CD163 correlated with tissue iron content but iron itself was not associated with the symptom status.
CONCLUSIONS—Symptomatic plaques show overexpression of CD163 and HO-1 both in intraindividual and interindividual comparison. Their expression correlates with iron deposits but asymptomatic and symptomatic plaques from isolated patients do not differ in macroscopic hemorrhages or iron deposits. We suggest that symptomatic plaques show a more pronounced induction of CD163 and HO-1 in response to plaque hemorrhages.</description><subject>Aged</subject><subject>Antigens, CD - genetics</subject><subject>Antigens, CD - metabolism</subject><subject>Antigens, Differentiation, Myelomonocytic - genetics</subject><subject>Antigens, Differentiation, Myelomonocytic - 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>Carotid Stenosis - genetics</subject><subject>Carotid Stenosis - metabolism</subject><subject>Carotid Stenosis - physiopathology</subject><subject>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</subject><subject>DNA - genetics</subject><subject>Female</subject><subject>Gene Expression Regulation</subject><subject>Heme - metabolism</subject><subject>Heme Oxygenase-1 - genetics</subject><subject>Heme Oxygenase-1 - metabolism</subject><subject>Hemorrhage</subject><subject>Humans</subject><subject>Iron - metabolism</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Neurology</subject><subject>Neurosurgery</subject><subject>Oligonucleotide Array Sequence Analysis - methods</subject><subject>Receptors, Cell Surface - genetics</subject><subject>Receptors, Cell Surface - metabolism</subject><subject>Receptors, Transferrin - genetics</subject><subject>Receptors, Transferrin - metabolism</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Skull, brain, vascular surgery</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Vascular diseases and vascular malformations of the nervous system</subject><issn>1079-5642</issn><issn>1524-4636</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkFtvEzEQRlcIRC_wF5CFBG-7nVnfeYsCtJWKgmjLCw-W452oC3tJ7U1L_j0OiRS_jC2dmc9ziuI9QoWo8AKwmt39rCCfWqK1WCmhUFekXxSnKGtRCsXVy3wHbUupRH1SnKX0O_OiruF1cYIarNRoT4tf39oQRx-j37LZ4LttahP7QU_ku8QWTxTp7zpSSu04sHHF5p9RceaHhl0tSmTtwG63_Xoaez-1gc19HKe2Yd87_7ih9KZ4tcpj6O2hnhf3X7_cza_Km8Xl9Xx2UwZhUZSNboCEEmSXARQZZTnIYJbaBA6W12AAlg1JQgIVpJE-WK8azbkGIRrg58XH_dx1HHe5k-vbFKjr_EDjJjlluDZo6gx-2oN55ZQirdw6tr2PW4fgdmodoMtq3VGt-6_Wkc7N7w4pm2VPzbH14DIDHw6AT8F3q-iH0KYjZwRIqEXmxJ57HruJYvrTbZ4puoesfHrYRQuuQJY1gAbMz3L3GcH_ARvBkE0</recordid><startdate>200701</startdate><enddate>200701</enddate><creator>Ijäs, Petra</creator><creator>Nuotio, Krista</creator><creator>Saksi, Jani</creator><creator>Soinne, Lauri</creator><creator>Saimanen, Eija</creator><creator>Karjalainen-Lindsberg, Marja-Liisa</creator><creator>Salonen, Oili</creator><creator>Sarna, Seppo</creator><creator>Tuimala, Jarno</creator><creator>Kovanen, Petri T</creator><creator>Kaste, Markku</creator><creator>Lindsberg, Perttu J</creator><general>American Heart Association, Inc</general><general>Lippincott</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>7X8</scope></search><sort><creationdate>200701</creationdate><title>Microarray Analysis Reveals Overexpression of CD163 and HO-1 in Symptomatic Carotid Plaques</title><author>Ijäs, Petra ; Nuotio, Krista ; Saksi, Jani ; Soinne, Lauri ; Saimanen, Eija ; Karjalainen-Lindsberg, Marja-Liisa ; Salonen, Oili ; Sarna, Seppo ; Tuimala, Jarno ; Kovanen, Petri T ; Kaste, Markku ; Lindsberg, Perttu J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4914-d7d0e464e9bc06e869305c8b78c309320800bde5e1e06c585ac9a6d7337044d03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Aged</topic><topic>Antigens, CD - genetics</topic><topic>Antigens, CD - metabolism</topic><topic>Antigens, Differentiation, Myelomonocytic - genetics</topic><topic>Antigens, Differentiation, Myelomonocytic - 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>Carotid Stenosis - genetics</topic><topic>Carotid Stenosis - metabolism</topic><topic>Carotid Stenosis - physiopathology</topic><topic>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</topic><topic>DNA - genetics</topic><topic>Female</topic><topic>Gene Expression Regulation</topic><topic>Heme - metabolism</topic><topic>Heme Oxygenase-1 - genetics</topic><topic>Heme Oxygenase-1 - metabolism</topic><topic>Hemorrhage</topic><topic>Humans</topic><topic>Iron - metabolism</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Neurology</topic><topic>Neurosurgery</topic><topic>Oligonucleotide Array Sequence Analysis - methods</topic><topic>Receptors, Cell Surface - genetics</topic><topic>Receptors, Cell Surface - metabolism</topic><topic>Receptors, Transferrin - genetics</topic><topic>Receptors, Transferrin - metabolism</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Skull, brain, vascular surgery</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</topic><topic>Vascular diseases and vascular malformations of the nervous system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ijäs, Petra</creatorcontrib><creatorcontrib>Nuotio, Krista</creatorcontrib><creatorcontrib>Saksi, Jani</creatorcontrib><creatorcontrib>Soinne, Lauri</creatorcontrib><creatorcontrib>Saimanen, Eija</creatorcontrib><creatorcontrib>Karjalainen-Lindsberg, Marja-Liisa</creatorcontrib><creatorcontrib>Salonen, Oili</creatorcontrib><creatorcontrib>Sarna, Seppo</creatorcontrib><creatorcontrib>Tuimala, Jarno</creatorcontrib><creatorcontrib>Kovanen, Petri T</creatorcontrib><creatorcontrib>Kaste, Markku</creatorcontrib><creatorcontrib>Lindsberg, Perttu J</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>MEDLINE - Academic</collection><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ijäs, Petra</au><au>Nuotio, Krista</au><au>Saksi, Jani</au><au>Soinne, Lauri</au><au>Saimanen, Eija</au><au>Karjalainen-Lindsberg, Marja-Liisa</au><au>Salonen, Oili</au><au>Sarna, Seppo</au><au>Tuimala, Jarno</au><au>Kovanen, Petri T</au><au>Kaste, Markku</au><au>Lindsberg, Perttu J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Microarray Analysis Reveals Overexpression of CD163 and HO-1 in Symptomatic Carotid Plaques</atitle><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle><addtitle>Arterioscler Thromb Vasc Biol</addtitle><date>2007-01</date><risdate>2007</risdate><volume>27</volume><issue>1</issue><spage>154</spage><epage>160</epage><pages>154-160</pages><issn>1079-5642</issn><eissn>1524-4636</eissn><coden>ATVBFA</coden><abstract>OBJECTIVE—We studied by microarray analysis whether symptomatic and asymptomatic carotid plaques from the same patient differ in gene expression and whether the same changes are present in an independent sample set.
METHODS AND RESULTS—Carotid plaques from four patients with bilateral high-grade stenosis, one being symptomatic and the other asymptomatic, were analyzed on Affymetrix U95Av2 arrays. 33 genes showed >1.5-fold change between symptomatic and asymptomatic plaques in an intraindividual comparison with FDR ranging from 0.28 to 0.40. Three genes involved in iron-heme homeostasis, CD163, HO-1, and transferrin receptor, were further analyzed in 40 independent plaques. HO-1 (fold-change 1.93, 95%CI 1.04 to 3.94, P=0.040) and CD163 (1.58, 1.11 to 2.40, P=0.013) mRNAs were again induced, and also HO-1 protein was overexpressed in symptomatic plaques (4.38, 1.54 to 12.20, P=0.024). The expression of HO-1 and CD163 correlated with tissue iron content but iron itself was not associated with the symptom status.
CONCLUSIONS—Symptomatic plaques show overexpression of CD163 and HO-1 both in intraindividual and interindividual comparison. Their expression correlates with iron deposits but asymptomatic and symptomatic plaques from isolated patients do not differ in macroscopic hemorrhages or iron deposits. We suggest that symptomatic plaques show a more pronounced induction of CD163 and HO-1 in response to plaque hemorrhages.</abstract><cop>Philadelphia, PA</cop><cop>Hagerstown, MD</cop><pub>American Heart Association, Inc</pub><pmid>17095719</pmid><doi>10.1161/01.ATV.0000251991.64617.e7</doi><tpages>7</tpages></addata></record> |
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subjects | Aged Antigens, CD - genetics Antigens, CD - metabolism Antigens, Differentiation, Myelomonocytic - genetics Antigens, Differentiation, Myelomonocytic - metabolism Atherosclerosis (general aspects, experimental research) Biological and medical sciences Blood and lymphatic vessels Cardiology. Vascular system Carotid Stenosis - genetics Carotid Stenosis - metabolism Carotid Stenosis - physiopathology Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous DNA - genetics Female Gene Expression Regulation Heme - metabolism Heme Oxygenase-1 - genetics Heme Oxygenase-1 - metabolism Hemorrhage Humans Iron - metabolism Male Medical sciences Middle Aged Neurology Neurosurgery Oligonucleotide Array Sequence Analysis - methods Receptors, Cell Surface - genetics Receptors, Cell Surface - metabolism Receptors, Transferrin - genetics Receptors, Transferrin - metabolism RNA, Messenger - genetics RNA, Messenger - metabolism Skull, brain, vascular surgery Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Vascular diseases and vascular malformations of the nervous system |
title | Microarray Analysis Reveals Overexpression of CD163 and HO-1 in Symptomatic Carotid Plaques |
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