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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A Combined Proteomic and Transcriptomic Approach Shows Diverging Molecular Mechanisms in Thoracic Aortic Aneurysm Development in Patients with Tricuspid- And Bicuspid Aortic Valve<xref ref-type="fn" rid="FN1">*</xref>
<xref ref-type="fn" rid="FN2"><sup><inline-graphic xlink:href="sbox.jpg"></inline-graphic>
</sup>
</xref>
</title>
<author><name sortKey="Kjellqvist, Sanela" sort="Kjellqvist, Sanela" uniqKey="Kjellqvist S" first="Sanela" last="Kjellqvist">Sanela Kjellqvist</name>
<affiliation><nlm:aff id="aff1">From the ‡Atherosclerosis Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Maleki, Shohreh" sort="Maleki, Shohreh" uniqKey="Maleki S" first="Shohreh" last="Maleki">Shohreh Maleki</name>
<affiliation><nlm:aff id="aff1">From the ‡Atherosclerosis Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Olsson, Therese" sort="Olsson, Therese" uniqKey="Olsson T" first="Therese" last="Olsson">Therese Olsson</name>
<affiliation><nlm:aff id="aff1">From the ‡Atherosclerosis Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chwastyniak, Maggy" sort="Chwastyniak, Maggy" uniqKey="Chwastyniak M" first="Maggy" last="Chwastyniak">Maggy Chwastyniak</name>
<affiliation><nlm:aff id="aff2">§Inserm U744, Institut Pasteur de Lille, University of Lille Nord de France, Lille, France;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Branca, Rui Miguel Mamede" sort="Branca, Rui Miguel Mamede" uniqKey="Branca R" first="Rui Miguel Mamede" last="Branca">Rui Miguel Mamede Branca</name>
<affiliation><nlm:aff id="aff3">¶Clinical Proteomics Mass Spectrometry, Department of Oncology-Pathology, Science for Life Laboratory and Karolinska Institutet, Stockholm, Sweden;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lehtio, Janne" sort="Lehtio, Janne" uniqKey="Lehtio J" first="Janne" last="Lehtiö">Janne Lehtiö</name>
<affiliation><nlm:aff id="aff3">¶Clinical Proteomics Mass Spectrometry, Department of Oncology-Pathology, Science for Life Laboratory and Karolinska Institutet, Stockholm, Sweden;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Pinet, Florence" sort="Pinet, Florence" uniqKey="Pinet F" first="Florence" last="Pinet">Florence Pinet</name>
<affiliation><nlm:aff id="aff2">§Inserm U744, Institut Pasteur de Lille, University of Lille Nord de France, Lille, France;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Franco Cereceda, Anders" sort="Franco Cereceda, Anders" uniqKey="Franco Cereceda A" first="Anders" last="Franco-Cereceda">Anders Franco-Cereceda</name>
<affiliation><nlm:aff id="aff4">‖Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Eriksson, Per" sort="Eriksson, Per" uniqKey="Eriksson P" first="Per" last="Eriksson">Per Eriksson</name>
<affiliation><nlm:aff id="aff1">From the ‡Atherosclerosis Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden;</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">23184916</idno>
<idno type="pmc">3567863</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3567863</idno>
<idno type="RBID">PMC:3567863</idno>
<idno type="doi">10.1074/mcp.M112.021873</idno>
<date when="2012">2012</date>
<idno type="wicri:Area/Pmc/Corpus">000513</idno>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A Combined Proteomic and Transcriptomic Approach Shows Diverging Molecular Mechanisms in Thoracic Aortic Aneurysm Development in Patients with Tricuspid- And Bicuspid Aortic Valve<xref ref-type="fn" rid="FN1">*</xref>
<xref ref-type="fn" rid="FN2"><sup><inline-graphic xlink:href="sbox.jpg"></inline-graphic>
</sup>
</xref>
</title>
<author><name sortKey="Kjellqvist, Sanela" sort="Kjellqvist, Sanela" uniqKey="Kjellqvist S" first="Sanela" last="Kjellqvist">Sanela Kjellqvist</name>
<affiliation><nlm:aff id="aff1">From the ‡Atherosclerosis Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Maleki, Shohreh" sort="Maleki, Shohreh" uniqKey="Maleki S" first="Shohreh" last="Maleki">Shohreh Maleki</name>
<affiliation><nlm:aff id="aff1">From the ‡Atherosclerosis Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Olsson, Therese" sort="Olsson, Therese" uniqKey="Olsson T" first="Therese" last="Olsson">Therese Olsson</name>
<affiliation><nlm:aff id="aff1">From the ‡Atherosclerosis Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chwastyniak, Maggy" sort="Chwastyniak, Maggy" uniqKey="Chwastyniak M" first="Maggy" last="Chwastyniak">Maggy Chwastyniak</name>
<affiliation><nlm:aff id="aff2">§Inserm U744, Institut Pasteur de Lille, University of Lille Nord de France, Lille, France;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Branca, Rui Miguel Mamede" sort="Branca, Rui Miguel Mamede" uniqKey="Branca R" first="Rui Miguel Mamede" last="Branca">Rui Miguel Mamede Branca</name>
<affiliation><nlm:aff id="aff3">¶Clinical Proteomics Mass Spectrometry, Department of Oncology-Pathology, Science for Life Laboratory and Karolinska Institutet, Stockholm, Sweden;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Lehtio, Janne" sort="Lehtio, Janne" uniqKey="Lehtio J" first="Janne" last="Lehtiö">Janne Lehtiö</name>
<affiliation><nlm:aff id="aff3">¶Clinical Proteomics Mass Spectrometry, Department of Oncology-Pathology, Science for Life Laboratory and Karolinska Institutet, Stockholm, Sweden;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Pinet, Florence" sort="Pinet, Florence" uniqKey="Pinet F" first="Florence" last="Pinet">Florence Pinet</name>
<affiliation><nlm:aff id="aff2">§Inserm U744, Institut Pasteur de Lille, University of Lille Nord de France, Lille, France;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Franco Cereceda, Anders" sort="Franco Cereceda, Anders" uniqKey="Franco Cereceda A" first="Anders" last="Franco-Cereceda">Anders Franco-Cereceda</name>
<affiliation><nlm:aff id="aff4">‖Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Eriksson, Per" sort="Eriksson, Per" uniqKey="Eriksson P" first="Per" last="Eriksson">Per Eriksson</name>
<affiliation><nlm:aff id="aff1">From the ‡Atherosclerosis Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden;</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Molecular & Cellular Proteomics : MCP</title>
<idno type="ISSN">1535-9476</idno>
<idno type="eISSN">1535-9484</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
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<front><div type="abstract" xml:lang="en"><p>Thoracic aortic aneurysm is a pathological local dilatation of the aorta, potentially leading to aortic rupture or dissection. The disease is a common complication of patients with bicuspid aortic valve, a congenital disorder present in 1–2% of the population. Using two dimensional fluorescence difference gel electrophoresis proteomics followed by mRNA expression, and alternative splicing analysis of the identified proteins, differences in dilated and nondilated aorta tissues between 44 patients with bicuspid and tricuspid valves was examined. The pattern of protein expression was successfully validated with LC-MS/MS. A multivariate analysis of protein expression data revealed diverging protein expression fingerprints in patients with tricuspid compared with the patients with bicuspid aortic valves. From 302 protein spots included in the analysis, 69 and 38 spots were differentially expressed between dilated and nondilated aorta specifically in patients with tricuspid and bicuspid aortic valve, respectively. 92 protein spots were differentially expressed between dilated and nondilated aorta in both phenotypes. Similarly, mRNA expression together with alternative splicing analysis of the identified proteins also showed diverging fingerprints in the two patient groups. Differential splicing was abundant but the expression levels of differentially spliced mRNA transcripts were low compared with the wild type transcript and there was no correlation between splicing and the number of spots. Therefore, the different spots are likely to represent post-translational modifications. The identification of differentially expressed proteins suggests that dilatation in patients with a tricuspid aortic valve involves inflammatory processes whereas aortic aneurysm in patients with BAV may be the consequence of impaired repair capacity. The results imply that aortic aneurysm formation in patients with bicuspid and tricuspid aortic valves involve different biological pathways leading to the same phenotype.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Mol Cell Proteomics</journal-id>
<journal-id journal-id-type="iso-abbrev">Mol. Cell Proteomics</journal-id>
<journal-id journal-id-type="hwp">mcprot</journal-id>
<journal-id journal-id-type="pmc">mcprot</journal-id>
<journal-id journal-id-type="publisher-id">MCP</journal-id>
<journal-title-group><journal-title>Molecular & Cellular Proteomics : MCP</journal-title>
</journal-title-group>
<issn pub-type="ppub">1535-9476</issn>
<issn pub-type="epub">1535-9484</issn>
<publisher><publisher-name>The American Society for Biochemistry and Molecular Biology</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">23184916</article-id>
<article-id pub-id-type="pmc">3567863</article-id>
<article-id pub-id-type="publisher-id">M112.021873</article-id>
<article-id pub-id-type="doi">10.1074/mcp.M112.021873</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research</subject>
</subj-group>
</article-categories>
<title-group><article-title>A Combined Proteomic and Transcriptomic Approach Shows Diverging Molecular Mechanisms in Thoracic Aortic Aneurysm Development in Patients with Tricuspid- And Bicuspid Aortic Valve<xref ref-type="fn" rid="FN1">*</xref>
<xref ref-type="fn" rid="FN2"><sup><inline-graphic xlink:href="sbox.jpg"></inline-graphic>
</sup>
</xref>
</article-title>
<alt-title alt-title-type="short">Diverging Molecular Mechanisms in Thoracic Aortic Aneurysm</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Kjellqvist</surname>
<given-names>Sanela</given-names>
</name>
<xref ref-type="aff" rid="aff1">‡</xref>
<xref ref-type="corresp" rid="cor1">**</xref>
<xref ref-type="author-notes" rid="FN3">‡‡</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Maleki</surname>
<given-names>Shohreh</given-names>
</name>
<xref ref-type="aff" rid="aff1">‡</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Olsson</surname>
<given-names>Therese</given-names>
</name>
<xref ref-type="aff" rid="aff1">‡</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chwastyniak</surname>
<given-names>Maggy</given-names>
</name>
<xref ref-type="aff" rid="aff2">§</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Branca</surname>
<given-names>Rui Miguel Mamede</given-names>
</name>
<xref ref-type="aff" rid="aff3">¶</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lehtiö</surname>
<given-names>Janne</given-names>
</name>
<xref ref-type="aff" rid="aff3">¶</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Pinet</surname>
<given-names>Florence</given-names>
</name>
<xref ref-type="aff" rid="aff2">§</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Franco-Cereceda</surname>
<given-names>Anders</given-names>
</name>
<xref ref-type="aff" rid="aff4">‖</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Eriksson</surname>
<given-names>Per</given-names>
</name>
<xref ref-type="aff" rid="aff1">‡</xref>
</contrib>
<aff id="aff1">From the ‡Atherosclerosis Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden;</aff>
<aff id="aff2">§Inserm U744, Institut Pasteur de Lille, University of Lille Nord de France, Lille, France;</aff>
<aff id="aff3">¶Clinical Proteomics Mass Spectrometry, Department of Oncology-Pathology, Science for Life Laboratory and Karolinska Institutet, Stockholm, Sweden;</aff>
<aff id="aff4">‖Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden</aff>
</contrib-group>
<author-notes><corresp id="cor1">** To whom correspondence should be addressed:
<addr-line>CMM, L8:03, Karolinska University Hospital, Solna, S-171 76 Stockholm, Sweden.</addr-line>
Tel.:
<phone>+46 8-51773828</phone>
; Fax:
<fax>+46 8-311 298</fax>
; E-mail: <email>sanela.kjellqvist@ki.se</email>
</corresp>
<fn fn-type="other" id="FN3"><p>‡‡ Formerly Sanela Kurtovic.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub"><month>2</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="epub"><day>26</day>
<month>11</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>1</day>
<month>2</month>
<year>2014</year>
</pub-date>
<pmc-comment> PMC Release delay is 12 months and 0 days and was based on the
. </pmc-comment>
<volume>12</volume>
<issue>2</issue>
<fpage>407</fpage>
<lpage>425</lpage>
<history><date date-type="received"><day>29</day>
<month>6</month>
<year>2012</year>
</date>
<date date-type="rev-recd"><day>3</day>
<month>11</month>
<year>2012</year>
</date>
</history>
<permissions><copyright-statement>© 2013 by The American Society for Biochemistry and Molecular Biology, Inc.</copyright-statement>
<copyright-year>2013</copyright-year>
</permissions>
<self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zjw00213000407.pdf"></self-uri>
<abstract><p>Thoracic aortic aneurysm is a pathological local dilatation of the aorta, potentially leading to aortic rupture or dissection. The disease is a common complication of patients with bicuspid aortic valve, a congenital disorder present in 1–2% of the population. Using two dimensional fluorescence difference gel electrophoresis proteomics followed by mRNA expression, and alternative splicing analysis of the identified proteins, differences in dilated and nondilated aorta tissues between 44 patients with bicuspid and tricuspid valves was examined. The pattern of protein expression was successfully validated with LC-MS/MS. A multivariate analysis of protein expression data revealed diverging protein expression fingerprints in patients with tricuspid compared with the patients with bicuspid aortic valves. From 302 protein spots included in the analysis, 69 and 38 spots were differentially expressed between dilated and nondilated aorta specifically in patients with tricuspid and bicuspid aortic valve, respectively. 92 protein spots were differentially expressed between dilated and nondilated aorta in both phenotypes. Similarly, mRNA expression together with alternative splicing analysis of the identified proteins also showed diverging fingerprints in the two patient groups. Differential splicing was abundant but the expression levels of differentially spliced mRNA transcripts were low compared with the wild type transcript and there was no correlation between splicing and the number of spots. Therefore, the different spots are likely to represent post-translational modifications. The identification of differentially expressed proteins suggests that dilatation in patients with a tricuspid aortic valve involves inflammatory processes whereas aortic aneurysm in patients with BAV may be the consequence of impaired repair capacity. The results imply that aortic aneurysm formation in patients with bicuspid and tricuspid aortic valves involve different biological pathways leading to the same phenotype.</p>
</abstract>
</article-meta>
</front>
</pmc>
</record>
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