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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Vildagliptin Stimulates Endothelial Cell Network Formation and Ischemia-induced Revascularization via an Endothelial Nitric-oxide Synthase-dependent Mechanism<xref ref-type="fn" rid="FN1">*</xref></title><author><name sortKey="Ishii, Masakazu" sort="Ishii, Masakazu" uniqKey="Ishii M" first="Masakazu" last="Ishii">Masakazu Ishii</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff4"></nlm:aff></affiliation></author><author><name sortKey="Shibata, Rei" sort="Shibata, Rei" uniqKey="Shibata R" first="Rei" last="Shibata">Rei Shibata</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Kondo, Kazuhisa" sort="Kondo, Kazuhisa" uniqKey="Kondo K" first="Kazuhisa" last="Kondo">Kazuhisa Kondo</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Kambara, Takahiro" sort="Kambara, Takahiro" uniqKey="Kambara T" first="Takahiro" last="Kambara">Takahiro Kambara</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Shimizu, Yuuki" sort="Shimizu, Yuuki" uniqKey="Shimizu Y" first="Yuuki" last="Shimizu">Yuuki Shimizu</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Tanigawa, Tohru" sort="Tanigawa, Tohru" uniqKey="Tanigawa T" first="Tohru" last="Tanigawa">Tohru Tanigawa</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Bando, Yasuko K" sort="Bando, Yasuko K" uniqKey="Bando Y" first="Yasuko K." last="Bando">Yasuko K. Bando</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Nishimura, Masahiro" sort="Nishimura, Masahiro" uniqKey="Nishimura M" first="Masahiro" last="Nishimura">Masahiro Nishimura</name><affiliation><nlm:aff id="aff4"></nlm:aff></affiliation></author><author><name sortKey="Ouchi, Noriyuki" sort="Ouchi, Noriyuki" uniqKey="Ouchi N" first="Noriyuki" last="Ouchi">Noriyuki Ouchi</name><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Murohara, Toyoaki" sort="Murohara, Toyoaki" uniqKey="Murohara T" first="Toyoaki" last="Murohara">Toyoaki Murohara</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25100725</idno><idno type="pmc">4175356</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175356</idno><idno type="RBID">PMC:4175356</idno><idno type="doi">10.1074/jbc.M114.557835</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">002E95</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002E95</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Vildagliptin Stimulates Endothelial Cell Network Formation and Ischemia-induced Revascularization via an Endothelial Nitric-oxide Synthase-dependent Mechanism<xref ref-type="fn" rid="FN1">*</xref></title><author><name sortKey="Ishii, Masakazu" sort="Ishii, Masakazu" uniqKey="Ishii M" first="Masakazu" last="Ishii">Masakazu Ishii</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff4"></nlm:aff></affiliation></author><author><name sortKey="Shibata, Rei" sort="Shibata, Rei" uniqKey="Shibata R" first="Rei" last="Shibata">Rei Shibata</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Kondo, Kazuhisa" sort="Kondo, Kazuhisa" uniqKey="Kondo K" first="Kazuhisa" last="Kondo">Kazuhisa Kondo</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Kambara, Takahiro" sort="Kambara, Takahiro" uniqKey="Kambara T" first="Takahiro" last="Kambara">Takahiro Kambara</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Shimizu, Yuuki" sort="Shimizu, Yuuki" uniqKey="Shimizu Y" first="Yuuki" last="Shimizu">Yuuki Shimizu</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Tanigawa, Tohru" sort="Tanigawa, Tohru" uniqKey="Tanigawa T" first="Tohru" last="Tanigawa">Tohru Tanigawa</name><affiliation><nlm:aff id="aff2"></nlm:aff></affiliation></author><author><name sortKey="Bando, Yasuko K" sort="Bando, Yasuko K" uniqKey="Bando Y" first="Yasuko K." last="Bando">Yasuko K. Bando</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Nishimura, Masahiro" sort="Nishimura, Masahiro" uniqKey="Nishimura M" first="Masahiro" last="Nishimura">Masahiro Nishimura</name><affiliation><nlm:aff id="aff4"></nlm:aff></affiliation></author><author><name sortKey="Ouchi, Noriyuki" sort="Ouchi, Noriyuki" uniqKey="Ouchi N" first="Noriyuki" last="Ouchi">Noriyuki Ouchi</name><affiliation><nlm:aff id="aff3"></nlm:aff></affiliation></author><author><name sortKey="Murohara, Toyoaki" sort="Murohara, Toyoaki" uniqKey="Murohara T" first="Toyoaki" last="Murohara">Toyoaki Murohara</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></analytic><series><title level="j">The Journal of Biological Chemistry</title><idno type="ISSN">0021-9258</idno><idno type="eISSN">1083-351X</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><bold>Background:</bold> DPP-4 inhibitors exert pleiotropic effects that modulate cardiovascular disease.</p><p><bold>Results:</bold> The DPP-4 inhibitor vildagliptin stimulates ischemia-induced revascularization through eNOS signaling. The angiogenic actions of vildagliptin are mediated by both GLP-1-dependent and -independent mechanisms.</p><p><bold>Conclusion:</bold> DPP-4 inhibitor promotes endothelial cell function via eNOS signaling.</p><p><bold>Significance:</bold> DPP-4 inhibitor could be beneficial in patients with diabetes-related vascular complications.</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">J Biol Chem</journal-id><journal-id journal-id-type="iso-abbrev">J. Biol. Chem</journal-id><journal-id journal-id-type="hwp">jbc</journal-id><journal-id journal-id-type="pmc">jbc</journal-id><journal-id journal-id-type="publisher-id">JBC</journal-id><journal-title-group><journal-title>The Journal of Biological Chemistry</journal-title></journal-title-group><issn pub-type="ppub">0021-9258</issn><issn pub-type="epub">1083-351X</issn><publisher><publisher-name>American Society for Biochemistry and Molecular Biology</publisher-name><publisher-loc>9650 Rockville Pike, Bethesda, MD 20814, U.S.A.</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">25100725</article-id><article-id pub-id-type="pmc">4175356</article-id><article-id pub-id-type="publisher-id">M114.557835</article-id><article-id pub-id-type="doi">10.1074/jbc.M114.557835</article-id><article-categories><subj-group subj-group-type="heading"><subject>Molecular Bases of Disease</subject></subj-group></article-categories><title-group><article-title>Vildagliptin Stimulates Endothelial Cell Network Formation and Ischemia-induced Revascularization via an Endothelial Nitric-oxide Synthase-dependent Mechanism<xref ref-type="fn" rid="FN1">*</xref></article-title><alt-title alt-title-type="short">Vildagliptin and Revascularization</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Ishii</surname><given-names>Masakazu</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="aff" rid="aff4"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Shibata</surname><given-names>Rei</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="corresp" rid="cor1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kondo</surname><given-names>Kazuhisa</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kambara</surname><given-names>Takahiro</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Shimizu</surname><given-names>Yuuki</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Tanigawa</surname><given-names>Tohru</given-names></name><xref ref-type="aff" rid="aff2"><sup>¶</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bando</surname><given-names>Yasuko K.</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Nishimura</surname><given-names>Masahiro</given-names></name><xref ref-type="aff" rid="aff4"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ouchi</surname><given-names>Noriyuki</given-names></name><xref ref-type="aff" rid="aff3"><sup>‖</sup></xref></contrib><contrib contrib-type="author"><name><surname>Murohara</surname><given-names>Toyoaki</given-names></name><xref ref-type="aff" rid="aff1"><sup>‡</sup></xref><xref ref-type="corresp" rid="cor2"><sup>2</sup></xref></contrib><aff id="aff1">From the<label>‡</label>Department of Cardiology, Nagoya University Graduate School of Medicine, 466-8550 Nagoya, Japan,</aff><aff id="aff2">the<label>¶</label>Department of Otolaryngology, Aichi Medical University, 480-1195 Nagakute, Japan,</aff><aff id="aff3">the<label>‖</label>Department of Molecular Cardiology, Nagoya University Graduate School of Medicine, 466-8550 Nagoya, Japan, and</aff><aff id="aff4">the<label>§</label>Department of Oral and Maxillofacial Prosthodontics, Kagoshima University Graduate school of Medical and Dental Science, 890-8544 Kagoshima, Japan</aff></contrib-group><author-notes><corresp id="cor1"><label>1</label> To whom correspondence may be addressed: <addr-line>Dept. of Cardiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Aichi, Nagoya 466-8550, Japan.</addr-line> Tel.: <phone>81-52-744-2147</phone>; Fax: <fax>81-52-744-2138</fax>; E-mail: <email>rshibata@med.nagoya-u.ac.jp</email>.</corresp><corresp id="cor2"><label>2</label> To whom correspondence may be addressed: <addr-line>Dept. of Cardiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Aichi, Nagoya 466-8550, Japan.</addr-line> Tel.: <phone>81-52-744-2147</phone>; Fax: <fax>81-52-744-2138</fax>; E-mail: <email>murohara@med.nagoya-u.ac.jp</email>.</corresp></author-notes><pub-date pub-type="ppub"><day>26</day><month>9</month><year>2014</year></pub-date><pub-date pub-type="epub"><day>6</day><month>8</month><year>2014</year></pub-date><volume>289</volume><issue>39</issue><fpage>27235</fpage><lpage>27245</lpage><history><date date-type="received"><day>13</day><month>2</month><year>2014</year></date><date date-type="rev-recd"><day>23</day><month>7</month><year>2014</year></date></history><permissions><copyright-statement>© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.</copyright-statement><copyright-year>2014</copyright-year></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zbc03914027235.pdf"></self-uri><abstract abstract-type="teaser"><p><bold>Background:</bold> DPP-4 inhibitors exert pleiotropic effects that modulate cardiovascular disease.</p><p><bold>Results:</bold> The DPP-4 inhibitor vildagliptin stimulates ischemia-induced revascularization through eNOS signaling. The angiogenic actions of vildagliptin are mediated by both GLP-1-dependent and -independent mechanisms.</p><p><bold>Conclusion:</bold> DPP-4 inhibitor promotes endothelial cell function via eNOS signaling.</p><p><bold>Significance:</bold> DPP-4 inhibitor could be beneficial in patients with diabetes-related vascular complications.</p></abstract><abstract><p>Dipeptidyl peptidase-4 inhibitors are known to lower glucose levels and are also beneficial in the management of cardiovascular disease. Here, we investigated whether a dipeptidyl peptidase-4 inhibitor, vildagliptin, modulates endothelial cell network formation and revascularization processes <italic>in vitro</italic> and <italic>in vivo</italic>. Treatment with vildagliptin enhanced blood flow recovery and capillary density in the ischemic limbs of wild-type mice, with accompanying increases in phosphorylation of Akt and endothelial nitric-oxide synthase (eNOS). In contrast to wild-type mice, treatment with vildagliptin did not improve blood flow in ischemic muscles of eNOS-deficient mice. Treatment with vildagliptin increased the levels of glucagon-like peptide-1 (GLP-1) and adiponectin, which have protective effects on the vasculature. Both vildagliptin and GLP-1 increased the differentiation of cultured human umbilical vein endothelial cells (HUVECs) into vascular-like structures, although vildagliptin was less effective than GLP-1. GLP-1 and vildagliptin also stimulated the phosphorylation of Akt and eNOS in HUVECs. Pretreatment with a PI3 kinase or NOS inhibitor blocked the stimulatory effects of both vildagliptin and GLP-1 on HUVEC differentiation. Furthermore, treatment with vildagliptin only partially increased the limb flow of ischemic muscle in adiponectin-deficient mice <italic>in vivo</italic>. GLP-1, but not vildagliptin, significantly increased adiponectin expression in differentiated 3T3-L1 adipocytes <italic>in vitro</italic>. These data indicate that vildagliptin promotes endothelial cell function via eNOS signaling, an effect that may be mediated by both GLP-1-dependent and GLP-1-independent mechanisms. The beneficial activity of GLP-1 for revascularization may also be partially mediated by its ability to increase adiponectin production.</p></abstract><kwd-group><kwd>Adiponectin</kwd><kwd>Angiogenesis</kwd><kwd>Endothelial Cell</kwd><kwd>Nitric-oxide Synthase</kwd><kwd>Signaling</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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