Mouse Strain–Specific Differences in Vascular Wall Gene Expression and Their Relationship to Vascular Disease

OBJECTIVE—Different strains of inbred mice exhibit different susceptibility to the development of atherosclerosis. The C3H/HeJ and C57Bl/6 mice have been used in several studies aimed at understanding the genetic basis of atherosclerosis. Under controlled environmental conditions, variations in susc...

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Veröffentlicht in:Arteriosclerosis, thrombosis, and vascular biology thrombosis, and vascular biology, 2005-02, Vol.25 (2), p.302-308
Hauptverfasser: Tabibiazar, Raymond, Wagner, Roger A, Spin, Joshua M, Ashley, Euan A, Narasimhan, Balasubramanian, Rubin, Edward M, Efron, Bradley, Tsao, Phil S, Tibshirani, Robert, Quertermous, Thomas
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container_issue 2
container_start_page 302
container_title Arteriosclerosis, thrombosis, and vascular biology
container_volume 25
creator Tabibiazar, Raymond
Wagner, Roger A
Spin, Joshua M
Ashley, Euan A
Narasimhan, Balasubramanian
Rubin, Edward M
Efron, Bradley
Tsao, Phil S
Tibshirani, Robert
Quertermous, Thomas
description OBJECTIVE—Different strains of inbred mice exhibit different susceptibility to the development of atherosclerosis. The C3H/HeJ and C57Bl/6 mice have been used in several studies aimed at understanding the genetic basis of atherosclerosis. Under controlled environmental conditions, variations in susceptibility to atherosclerosis reflect differences in genetic makeup, and these differences must be reflected in gene expression patterns that are temporally related to the development of disease. In this study, we sought to identify the genetic pathways that are differentially activated in the aortas of these mice. METHODS AND RESULTS—We performed genome-wide transcriptional profiling of aortas from C3H/HeJ and C57Bl/6 mice. Differences in gene expression were identified at baseline as well as during normal aging and longitudinal exposure to high-fat diet. The significance of these genes to the development of atherosclerosis was evaluated by observing their temporal pattern of expression in the well-studied apolipoprotein E model of atherosclerosis. CONCLUSION—Gene expression differences between the 2 strains suggest that aortas of C57Bl/6 mice have a higher genetic propensity to develop inflammation in response to appropriate atherogenic stimuli. This study expands the repertoire of factors in known disease-related signaling pathways and identifies novel candidate genes for future study.
doi_str_mv 10.1161/01.ATV.0000151372.86863.a5
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The C3H/HeJ and C57Bl/6 mice have been used in several studies aimed at understanding the genetic basis of atherosclerosis. Under controlled environmental conditions, variations in susceptibility to atherosclerosis reflect differences in genetic makeup, and these differences must be reflected in gene expression patterns that are temporally related to the development of disease. In this study, we sought to identify the genetic pathways that are differentially activated in the aortas of these mice. METHODS AND RESULTS—We performed genome-wide transcriptional profiling of aortas from C3H/HeJ and C57Bl/6 mice. Differences in gene expression were identified at baseline as well as during normal aging and longitudinal exposure to high-fat diet. The significance of these genes to the development of atherosclerosis was evaluated by observing their temporal pattern of expression in the well-studied apolipoprotein E model of atherosclerosis. CONCLUSION—Gene expression differences between the 2 strains suggest that aortas of C57Bl/6 mice have a higher genetic propensity to develop inflammation in response to appropriate atherogenic stimuli. This study expands the repertoire of factors in known disease-related signaling pathways and identifies novel candidate genes for future study.</description><identifier>ISSN: 1079-5642</identifier><identifier>EISSN: 1524-4636</identifier><identifier>DOI: 10.1161/01.ATV.0000151372.86863.a5</identifier><identifier>PMID: 15550693</identifier><identifier>CODEN: ATVBFA</identifier><language>eng</language><publisher>Philadelphia, PA: American Heart Association, Inc</publisher><subject>Aging - genetics ; Aging - metabolism ; Animals ; Aorta - metabolism ; Aorta - pathology ; Aortitis - genetics ; Aortitis - metabolism ; Aortitis - pathology ; Apolipoproteins E - deficiency ; Apolipoproteins E - genetics ; Arteriosclerosis - genetics ; Arteriosclerosis - metabolism ; Arteriosclerosis - pathology ; Atherosclerosis (general aspects, experimental research) ; Biological and medical sciences ; Blood and lymphatic vessels ; Blood vessels and receptors ; Cardiology. Vascular system ; Diet, Atherogenic ; Dietary Fats - pharmacology ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; Female ; Fundamental and applied biological sciences. Psychology ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Genetic Predisposition to Disease ; Inflammation - genetics ; Medical sciences ; Mice ; Mice, Inbred C3H - genetics ; Mice, Inbred C3H - metabolism ; Mice, Inbred C57BL - genetics ; Mice, Inbred C57BL - metabolism ; Mice, Knockout ; Oligonucleotide Array Sequence Analysis ; Reverse Transcriptase Polymerase Chain Reaction ; Transcription, Genetic ; Vertebrates: cardiovascular system</subject><ispartof>Arteriosclerosis, thrombosis, and vascular biology, 2005-02, Vol.25 (2), p.302-308</ispartof><rights>2005 American Heart Association, Inc.</rights><rights>2005 INIST-CNRS</rights><rights>Copyright American Heart Association, Inc. 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The C3H/HeJ and C57Bl/6 mice have been used in several studies aimed at understanding the genetic basis of atherosclerosis. Under controlled environmental conditions, variations in susceptibility to atherosclerosis reflect differences in genetic makeup, and these differences must be reflected in gene expression patterns that are temporally related to the development of disease. In this study, we sought to identify the genetic pathways that are differentially activated in the aortas of these mice. METHODS AND RESULTS—We performed genome-wide transcriptional profiling of aortas from C3H/HeJ and C57Bl/6 mice. Differences in gene expression were identified at baseline as well as during normal aging and longitudinal exposure to high-fat diet. The significance of these genes to the development of atherosclerosis was evaluated by observing their temporal pattern of expression in the well-studied apolipoprotein E model of atherosclerosis. CONCLUSION—Gene expression differences between the 2 strains suggest that aortas of C57Bl/6 mice have a higher genetic propensity to develop inflammation in response to appropriate atherogenic stimuli. 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Psychology</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Developmental</topic><topic>Genetic Predisposition to Disease</topic><topic>Inflammation - genetics</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C3H - genetics</topic><topic>Mice, Inbred C3H - metabolism</topic><topic>Mice, Inbred C57BL - genetics</topic><topic>Mice, Inbred C57BL - metabolism</topic><topic>Mice, Knockout</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Transcription, Genetic</topic><topic>Vertebrates: cardiovascular system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tabibiazar, Raymond</creatorcontrib><creatorcontrib>Wagner, Roger A</creatorcontrib><creatorcontrib>Spin, Joshua M</creatorcontrib><creatorcontrib>Ashley, Euan A</creatorcontrib><creatorcontrib>Narasimhan, Balasubramanian</creatorcontrib><creatorcontrib>Rubin, Edward M</creatorcontrib><creatorcontrib>Efron, Bradley</creatorcontrib><creatorcontrib>Tsao, Phil S</creatorcontrib><creatorcontrib>Tibshirani, Robert</creatorcontrib><creatorcontrib>Quertermous, Thomas</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 Health &amp; Medical Complete (Alumni)</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>Tabibiazar, Raymond</au><au>Wagner, Roger A</au><au>Spin, Joshua M</au><au>Ashley, Euan A</au><au>Narasimhan, Balasubramanian</au><au>Rubin, Edward M</au><au>Efron, Bradley</au><au>Tsao, Phil S</au><au>Tibshirani, Robert</au><au>Quertermous, Thomas</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mouse Strain–Specific Differences in Vascular Wall Gene Expression and Their Relationship to Vascular Disease</atitle><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle><addtitle>Arterioscler Thromb Vasc Biol</addtitle><date>2005-02</date><risdate>2005</risdate><volume>25</volume><issue>2</issue><spage>302</spage><epage>308</epage><pages>302-308</pages><issn>1079-5642</issn><eissn>1524-4636</eissn><coden>ATVBFA</coden><abstract>OBJECTIVE—Different strains of inbred mice exhibit different susceptibility to the development of atherosclerosis. The C3H/HeJ and C57Bl/6 mice have been used in several studies aimed at understanding the genetic basis of atherosclerosis. Under controlled environmental conditions, variations in susceptibility to atherosclerosis reflect differences in genetic makeup, and these differences must be reflected in gene expression patterns that are temporally related to the development of disease. In this study, we sought to identify the genetic pathways that are differentially activated in the aortas of these mice. METHODS AND RESULTS—We performed genome-wide transcriptional profiling of aortas from C3H/HeJ and C57Bl/6 mice. Differences in gene expression were identified at baseline as well as during normal aging and longitudinal exposure to high-fat diet. The significance of these genes to the development of atherosclerosis was evaluated by observing their temporal pattern of expression in the well-studied apolipoprotein E model of atherosclerosis. CONCLUSION—Gene expression differences between the 2 strains suggest that aortas of C57Bl/6 mice have a higher genetic propensity to develop inflammation in response to appropriate atherogenic stimuli. This study expands the repertoire of factors in known disease-related signaling pathways and identifies novel candidate genes for future study.</abstract><cop>Philadelphia, PA</cop><cop>Hagerstown, MD</cop><pub>American Heart Association, Inc</pub><pmid>15550693</pmid><doi>10.1161/01.ATV.0000151372.86863.a5</doi><tpages>7</tpages></addata></record>
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subjects Aging - genetics
Aging - metabolism
Animals
Aorta - metabolism
Aorta - pathology
Aortitis - genetics
Aortitis - metabolism
Aortitis - pathology
Apolipoproteins E - deficiency
Apolipoproteins E - genetics
Arteriosclerosis - genetics
Arteriosclerosis - metabolism
Arteriosclerosis - pathology
Atherosclerosis (general aspects, experimental research)
Biological and medical sciences
Blood and lymphatic vessels
Blood vessels and receptors
Cardiology. Vascular system
Diet, Atherogenic
Dietary Fats - pharmacology
Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous
Female
Fundamental and applied biological sciences. Psychology
Gene Expression Profiling
Gene Expression Regulation, Developmental
Genetic Predisposition to Disease
Inflammation - genetics
Medical sciences
Mice
Mice, Inbred C3H - genetics
Mice, Inbred C3H - metabolism
Mice, Inbred C57BL - genetics
Mice, Inbred C57BL - metabolism
Mice, Knockout
Oligonucleotide Array Sequence Analysis
Reverse Transcriptase Polymerase Chain Reaction
Transcription, Genetic
Vertebrates: cardiovascular system
title Mouse Strain–Specific Differences in Vascular Wall Gene Expression and Their Relationship to Vascular Disease
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