Adipocyte-Derived Microvesicles Are Associated with Multiple Angiogenic Factors and Induce Angiogenesis in Vivo and in Vitro
We previously reported that 3T3-L1 and rat primary adipocytes secreted microvesicles, known as adipocyte-derived microvesicles (ADMs). In the present study, we further characterized the 3T3-L1 ADMs and found that they exhibited angiogenic activity in vivo. Antibody arrays and gelatin zymography anal...
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| Veröffentlicht in: | Endocrinology (Philadelphia) 2010-06, Vol.151 (6), p.2567-2576 |
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| creator | Aoki, Naohito Yokoyama, Rumi Asai, Noriyuki Ohki, Makiko Ohki, Yuichi Kusubata, Kaori Heissig, Beate Hattori, Koichi Nakagawa, Yoshimi Matsuda, Tsukasa |
| description | We previously reported that 3T3-L1 and rat primary adipocytes secreted microvesicles, known as adipocyte-derived microvesicles (ADMs). In the present study, we further characterized the 3T3-L1 ADMs and found that they exhibited angiogenic activity in vivo. Antibody arrays and gelatin zymography analyses revealed that several angiogenic and antiangiogenic proteins, including leptin, TNFα, acidic fibroblast growth factor (FGFa), interferon-γ, and matrix metalloprotease (MMP)-2 and MMP-9, were present in the ADMs. Gene expression of most of these angiogenic factors was induced in the adipose tissue of diet-induced obese mice. Furthermore, leptin, TNFα, and MMP-2 were up-regulated at the protein level in the adipocyte fractions prepared from epididymal adipose tissues of high-fat-diet-induced obese mice. ADMs induced cell migration and tube formation of human umbilical vein endothelial cells, which were partially suppressed by neutralizing antibodies to leptin, TNFα, or FGFa but not to interferon-γ. Supporting these data, a mixture of leptin, TNFα, and FGFa induced tube formation. ADMs also promoted cell invasion of human umbilical vein endothelial cells through Matrigel, which was suppressed by the addition of the MMP inhibitor 1,10′-phenanthroline and a neutralizing antibody to MMP-2 but not to MMP-9. These results suggest that ADMs are associated with multiple angiogenic factors and play a role in angiogenesis in adipose tissue.
Adipocyte-derived microvesicles are associated with multiple angiogenic factors and exhibit angiogenic activity in vivo and in vitro. |
| doi_str_mv | 10.1210/en.2009-1023 |
| format | Article |
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Adipocyte-derived microvesicles are associated with multiple angiogenic factors and exhibit angiogenic activity in vivo and in vitro.</description><identifier>ISSN: 0013-7227</identifier><identifier>EISSN: 1945-7170</identifier><identifier>DOI: 10.1210/en.2009-1023</identifier><identifier>PMID: 20382694</identifier><identifier>CODEN: ENDOAO</identifier><language>eng</language><publisher>Chevy Chase, MD: Endocrine Society</publisher><subject>3T3-L1 Cells ; Adipocytes ; Adipocytes - metabolism ; Adipose tissue ; Angiogenesis ; Angiogenesis inhibitors ; Animals ; Antibodies ; Biological and medical sciences ; Body fat ; Cell Line ; Cell migration ; Cell Movement - physiology ; Cell-Derived Microparticles - metabolism ; Diet ; Electrophoresis, Polyacrylamide Gel ; Endothelial cells ; Endothelial Cells - cytology ; Fibroblast growth factor 1 ; Fibroblast Growth Factors - metabolism ; Fractions ; Fundamental and applied biological sciences. Psychology ; Gelatin ; Gelatinase A ; Gelatinase B ; Gene expression ; Growth factors ; High fat diet ; High protein diet ; Humans ; Immunoblotting ; In vivo methods and tests ; Interferon ; Interferon-gamma - metabolism ; Leptin ; Leptin - metabolism ; Male ; Matrix metalloproteinase ; Matrix Metalloproteinase 2 - metabolism ; Mice ; Mice, Inbred C57BL ; Neovascularization, Physiologic - physiology ; Neutralizing ; Polymerase Chain Reaction ; Proteins ; Tumor Necrosis Factor-alpha - metabolism ; Tumor necrosis factor-α ; Umbilical vein ; Umbilical Veins - cytology ; Vertebrates: endocrinology ; γ-Interferon</subject><ispartof>Endocrinology (Philadelphia), 2010-06, Vol.151 (6), p.2567-2576</ispartof><rights>Copyright © 2010 by the Endocrine Society 2010</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2010 by the Endocrine Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c462t-f6516765f435ee5c2c818f43e63c8dadccd055441bd17fb6497094682b48e233</citedby><cites>FETCH-LOGICAL-c462t-f6516765f435ee5c2c818f43e63c8dadccd055441bd17fb6497094682b48e233</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22885604$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20382694$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Aoki, Naohito</creatorcontrib><creatorcontrib>Yokoyama, Rumi</creatorcontrib><creatorcontrib>Asai, Noriyuki</creatorcontrib><creatorcontrib>Ohki, Makiko</creatorcontrib><creatorcontrib>Ohki, Yuichi</creatorcontrib><creatorcontrib>Kusubata, Kaori</creatorcontrib><creatorcontrib>Heissig, Beate</creatorcontrib><creatorcontrib>Hattori, Koichi</creatorcontrib><creatorcontrib>Nakagawa, Yoshimi</creatorcontrib><creatorcontrib>Matsuda, Tsukasa</creatorcontrib><title>Adipocyte-Derived Microvesicles Are Associated with Multiple Angiogenic Factors and Induce Angiogenesis in Vivo and in Vitro</title><title>Endocrinology (Philadelphia)</title><addtitle>Endocrinology</addtitle><description>We previously reported that 3T3-L1 and rat primary adipocytes secreted microvesicles, known as adipocyte-derived microvesicles (ADMs). In the present study, we further characterized the 3T3-L1 ADMs and found that they exhibited angiogenic activity in vivo. Antibody arrays and gelatin zymography analyses revealed that several angiogenic and antiangiogenic proteins, including leptin, TNFα, acidic fibroblast growth factor (FGFa), interferon-γ, and matrix metalloprotease (MMP)-2 and MMP-9, were present in the ADMs. Gene expression of most of these angiogenic factors was induced in the adipose tissue of diet-induced obese mice. Furthermore, leptin, TNFα, and MMP-2 were up-regulated at the protein level in the adipocyte fractions prepared from epididymal adipose tissues of high-fat-diet-induced obese mice. ADMs induced cell migration and tube formation of human umbilical vein endothelial cells, which were partially suppressed by neutralizing antibodies to leptin, TNFα, or FGFa but not to interferon-γ. Supporting these data, a mixture of leptin, TNFα, and FGFa induced tube formation. ADMs also promoted cell invasion of human umbilical vein endothelial cells through Matrigel, which was suppressed by the addition of the MMP inhibitor 1,10′-phenanthroline and a neutralizing antibody to MMP-2 but not to MMP-9. These results suggest that ADMs are associated with multiple angiogenic factors and play a role in angiogenesis in adipose tissue.
Adipocyte-derived microvesicles are associated with multiple angiogenic factors and exhibit angiogenic activity in vivo and in vitro.</description><subject>3T3-L1 Cells</subject><subject>Adipocytes</subject><subject>Adipocytes - metabolism</subject><subject>Adipose tissue</subject><subject>Angiogenesis</subject><subject>Angiogenesis inhibitors</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Biological and medical sciences</subject><subject>Body fat</subject><subject>Cell Line</subject><subject>Cell migration</subject><subject>Cell Movement - physiology</subject><subject>Cell-Derived Microparticles - metabolism</subject><subject>Diet</subject><subject>Electrophoresis, Polyacrylamide Gel</subject><subject>Endothelial cells</subject><subject>Endothelial Cells - cytology</subject><subject>Fibroblast growth factor 1</subject><subject>Fibroblast Growth Factors - metabolism</subject><subject>Fractions</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gelatin</subject><subject>Gelatinase A</subject><subject>Gelatinase B</subject><subject>Gene expression</subject><subject>Growth factors</subject><subject>High fat diet</subject><subject>High protein diet</subject><subject>Humans</subject><subject>Immunoblotting</subject><subject>In vivo methods and tests</subject><subject>Interferon</subject><subject>Interferon-gamma - metabolism</subject><subject>Leptin</subject><subject>Leptin - metabolism</subject><subject>Male</subject><subject>Matrix metalloproteinase</subject><subject>Matrix Metalloproteinase 2 - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Neovascularization, Physiologic - physiology</subject><subject>Neutralizing</subject><subject>Polymerase Chain Reaction</subject><subject>Proteins</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><subject>Tumor necrosis factor-α</subject><subject>Umbilical vein</subject><subject>Umbilical Veins - cytology</subject><subject>Vertebrates: endocrinology</subject><subject>γ-Interferon</subject><issn>0013-7227</issn><issn>1945-7170</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc1rFDEYxoNY7Fq9eZaAiBen5jszx6VaLbR4KV5DNnmnpswmYzKzUvCPN9tdXSjtKXl5fjzvx4PQG0pOKaPkE8RTRkjXUML4M7SgnZCNppo8RwtCKG80Y_oYvSzltpZCCP4CHTPCW6Y6sUB_lj6Myd1N0HyGHDbg8VVwOW2gBDdAwcsMeFlKcsFOVfwdpp_4ah6mMA5ViDch3UAMDp9bN6VcsI0eX0Q_u4NarQoOEf8Im3Sv3_-nnF6ho94OBV7v3xN0ff7l-uxbc_n968XZ8rJxQrGp6ZWkSivZCy4BpGOupW0tQHHXeuud80RKIejKU92vlOg06YRq2Uq0wDg_QR92tmNOv2Yok1mH4mAYbIQ0F6M5l4Rw2VXy3QPyNs051tkMp5woIone-n3cUfVOpWTozZjD2uY7Q4nZZmIgmm0mZptJxd_uTefVGvx_-F8IFXi_B2xxduizjS6UA8faVioiDnukeXyqZbNvyXckRJ9cDhHGDKUctnl00L-dArCM</recordid><startdate>20100601</startdate><enddate>20100601</enddate><creator>Aoki, Naohito</creator><creator>Yokoyama, Rumi</creator><creator>Asai, Noriyuki</creator><creator>Ohki, Makiko</creator><creator>Ohki, Yuichi</creator><creator>Kusubata, Kaori</creator><creator>Heissig, Beate</creator><creator>Hattori, Koichi</creator><creator>Nakagawa, Yoshimi</creator><creator>Matsuda, Tsukasa</creator><general>Endocrine Society</general><general>Oxford University Press</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>7QG</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20100601</creationdate><title>Adipocyte-Derived Microvesicles Are Associated with Multiple Angiogenic Factors and Induce Angiogenesis in Vivo and in Vitro</title><author>Aoki, Naohito ; Yokoyama, Rumi ; Asai, Noriyuki ; Ohki, Makiko ; Ohki, Yuichi ; Kusubata, Kaori ; Heissig, Beate ; Hattori, Koichi ; Nakagawa, Yoshimi ; Matsuda, Tsukasa</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c462t-f6516765f435ee5c2c818f43e63c8dadccd055441bd17fb6497094682b48e233</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>3T3-L1 Cells</topic><topic>Adipocytes</topic><topic>Adipocytes - metabolism</topic><topic>Adipose tissue</topic><topic>Angiogenesis</topic><topic>Angiogenesis inhibitors</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Biological and medical sciences</topic><topic>Body fat</topic><topic>Cell Line</topic><topic>Cell migration</topic><topic>Cell Movement - physiology</topic><topic>Cell-Derived Microparticles - metabolism</topic><topic>Diet</topic><topic>Electrophoresis, Polyacrylamide Gel</topic><topic>Endothelial cells</topic><topic>Endothelial Cells - cytology</topic><topic>Fibroblast growth factor 1</topic><topic>Fibroblast Growth Factors - metabolism</topic><topic>Fractions</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gelatin</topic><topic>Gelatinase A</topic><topic>Gelatinase B</topic><topic>Gene expression</topic><topic>Growth factors</topic><topic>High fat diet</topic><topic>High protein diet</topic><topic>Humans</topic><topic>Immunoblotting</topic><topic>In vivo methods and tests</topic><topic>Interferon</topic><topic>Interferon-gamma - metabolism</topic><topic>Leptin</topic><topic>Leptin - metabolism</topic><topic>Male</topic><topic>Matrix metalloproteinase</topic><topic>Matrix Metalloproteinase 2 - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Neovascularization, Physiologic - physiology</topic><topic>Neutralizing</topic><topic>Polymerase Chain Reaction</topic><topic>Proteins</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><topic>Tumor necrosis factor-α</topic><topic>Umbilical vein</topic><topic>Umbilical Veins - cytology</topic><topic>Vertebrates: endocrinology</topic><topic>γ-Interferon</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Aoki, Naohito</creatorcontrib><creatorcontrib>Yokoyama, Rumi</creatorcontrib><creatorcontrib>Asai, Noriyuki</creatorcontrib><creatorcontrib>Ohki, Makiko</creatorcontrib><creatorcontrib>Ohki, Yuichi</creatorcontrib><creatorcontrib>Kusubata, Kaori</creatorcontrib><creatorcontrib>Heissig, Beate</creatorcontrib><creatorcontrib>Hattori, Koichi</creatorcontrib><creatorcontrib>Nakagawa, Yoshimi</creatorcontrib><creatorcontrib>Matsuda, Tsukasa</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>Animal Behavior Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Endocrinology (Philadelphia)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Aoki, Naohito</au><au>Yokoyama, Rumi</au><au>Asai, Noriyuki</au><au>Ohki, Makiko</au><au>Ohki, Yuichi</au><au>Kusubata, Kaori</au><au>Heissig, Beate</au><au>Hattori, Koichi</au><au>Nakagawa, Yoshimi</au><au>Matsuda, Tsukasa</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Adipocyte-Derived Microvesicles Are Associated with Multiple Angiogenic Factors and Induce Angiogenesis in Vivo and in Vitro</atitle><jtitle>Endocrinology (Philadelphia)</jtitle><addtitle>Endocrinology</addtitle><date>2010-06-01</date><risdate>2010</risdate><volume>151</volume><issue>6</issue><spage>2567</spage><epage>2576</epage><pages>2567-2576</pages><issn>0013-7227</issn><eissn>1945-7170</eissn><coden>ENDOAO</coden><abstract>We previously reported that 3T3-L1 and rat primary adipocytes secreted microvesicles, known as adipocyte-derived microvesicles (ADMs). In the present study, we further characterized the 3T3-L1 ADMs and found that they exhibited angiogenic activity in vivo. Antibody arrays and gelatin zymography analyses revealed that several angiogenic and antiangiogenic proteins, including leptin, TNFα, acidic fibroblast growth factor (FGFa), interferon-γ, and matrix metalloprotease (MMP)-2 and MMP-9, were present in the ADMs. Gene expression of most of these angiogenic factors was induced in the adipose tissue of diet-induced obese mice. Furthermore, leptin, TNFα, and MMP-2 were up-regulated at the protein level in the adipocyte fractions prepared from epididymal adipose tissues of high-fat-diet-induced obese mice. ADMs induced cell migration and tube formation of human umbilical vein endothelial cells, which were partially suppressed by neutralizing antibodies to leptin, TNFα, or FGFa but not to interferon-γ. Supporting these data, a mixture of leptin, TNFα, and FGFa induced tube formation. ADMs also promoted cell invasion of human umbilical vein endothelial cells through Matrigel, which was suppressed by the addition of the MMP inhibitor 1,10′-phenanthroline and a neutralizing antibody to MMP-2 but not to MMP-9. These results suggest that ADMs are associated with multiple angiogenic factors and play a role in angiogenesis in adipose tissue.
Adipocyte-derived microvesicles are associated with multiple angiogenic factors and exhibit angiogenic activity in vivo and in vitro.</abstract><cop>Chevy Chase, MD</cop><pub>Endocrine Society</pub><pmid>20382694</pmid><doi>10.1210/en.2009-1023</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 3T3-L1 Cells Adipocytes Adipocytes - metabolism Adipose tissue Angiogenesis Angiogenesis inhibitors Animals Antibodies Biological and medical sciences Body fat Cell Line Cell migration Cell Movement - physiology Cell-Derived Microparticles - metabolism Diet Electrophoresis, Polyacrylamide Gel Endothelial cells Endothelial Cells - cytology Fibroblast growth factor 1 Fibroblast Growth Factors - metabolism Fractions Fundamental and applied biological sciences. Psychology Gelatin Gelatinase A Gelatinase B Gene expression Growth factors High fat diet High protein diet Humans Immunoblotting In vivo methods and tests Interferon Interferon-gamma - metabolism Leptin Leptin - metabolism Male Matrix metalloproteinase Matrix Metalloproteinase 2 - metabolism Mice Mice, Inbred C57BL Neovascularization, Physiologic - physiology Neutralizing Polymerase Chain Reaction Proteins Tumor Necrosis Factor-alpha - metabolism Tumor necrosis factor-α Umbilical vein Umbilical Veins - cytology Vertebrates: endocrinology γ-Interferon |
| title | Adipocyte-Derived Microvesicles Are Associated with Multiple Angiogenic Factors and Induce Angiogenesis in Vivo and in Vitro |
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