Expression of ADAMTS13 in Normal and Abnormal Placentae and Its Potential Role in Angiogenesis and Placenta Development

OBJECTIVE—ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 repeats, member 13) is primarily synthesized in liver. The biosynthesis of ADAMTS13 and its physiological role in placenta are not known. APPROACH AND RESULTS—We used real-time polymerase chain reaction, immunohistoch...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Arteriosclerosis, thrombosis, and vascular biology thrombosis, and vascular biology, 2017-09, Vol.37 (9), p.1748-1756
Hauptverfasser: Xiao, Juan, Feng, Yun, Li, Xueyin, Li, Wei, Fan, Lei, Liu, Jing, Zeng, Xue, Chen, Kaiyue, Chen, Xi, Zhou, Xiaoshui, Zheng, X Long, Chen, Suhua
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 1756
container_issue 9
container_start_page 1748
container_title Arteriosclerosis, thrombosis, and vascular biology
container_volume 37
creator Xiao, Juan
Feng, Yun
Li, Xueyin
Li, Wei
Fan, Lei
Liu, Jing
Zeng, Xue
Chen, Kaiyue
Chen, Xi
Zhou, Xiaoshui
Zheng, X Long
Chen, Suhua
description OBJECTIVE—ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 repeats, member 13) is primarily synthesized in liver. The biosynthesis of ADAMTS13 and its physiological role in placenta are not known. APPROACH AND RESULTS—We used real-time polymerase chain reaction, immunohistochemistry, and Western blotting analyses, as well as proteolytic cleavage of FRETS (fluorescent resonance energy transfers)-VWF73, to determine ADAMTS13 expression in placenta and trophoblasts obtained from individuals with normal pregnancy and patients with severe preeclampsia. We also determined the role of ADAMTS13 in extravillous trophoblasts using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, wound scratch assay, transwell migration assay, tube formation assay, and tissue outgrowth assays. We showed that full-length and proteolytically active ADAMTS13 was expressed in normal human placenta, primarily in the trophoblasts and villous core fetal vessel endothelium during pregnancy. Placental expression of ADAMTS13 mRNA, protein, and proteolytic activity was at the highest levels during the first trimester and significantly reduced at the term of gestation. Additionally, significantly reduced levels of placental ADAMTS13 expression was detected under hypoxic conditions and in patients with preeclampsia. In addition, recombinant ADAMTS13 protease stimulated proliferation, migration, invasion, and network formation of trophoblastic cells in culture. Finally, knockdown of ADAMTS13 expression attenuated the ability of tube formation in trophoblast (HTR-8/SVNEO) cells and the extravillous trophoblast outgrowth in placental explants. CONCLUSIONS—Our results demonstrate for the first time the expression of ADAMTS13 mRNA and protein in normal and abnormal placental tissues and its role in promoting angiogenesis and trophoblastic cell development. The findings support the potential role of the ADAMTS13–von Willebrand factor pathway in normal pregnancy and pathogenesis of preeclampsia.
doi_str_mv 10.1161/ATVBAHA.117.309735
format Article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5570641</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1924599413</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5155-ee118b191f8179d6d38286ed32b135719876dc594830c99bc885b3ae0439fc933</originalsourceid><addsrcrecordid>eNp9UU1v1DAUtBCIlsIf4IBy5JLij_jrghTa0lYqUMHC1XKSl12DE2_tbLf8e7zNtoILJ3vem5k30iD0muBjQgR5Vy9-fKgv6gzkMcNaMv4EHRJOq7ISTDzNfyx1yUVFD9CLlH5ijCtK8XN0QJXkhMvqEG3P7tYRUnJhLEJf1Kf1p8U3wgo3Fp9DHKwv7NgVdTPO4NrbFsbJwv34ckrFdZjywOXd1-Bhp6vHpQtLGCG5dE97EBWncAs-rIcMXqJnvfUJXu3fI_T949ni5KK8-nJ-eVJflW0OyEsAQlRDNOkVkboTHVNUCegYbQjjkmglRddyXSmGW62bVineMAu4YrpvNWNH6P3su940A3S7HNF6s45usPG3CdaZfzejW5lluDWcSywqkg3e7g1iuNlAmszgUgve2xHCJhmiacW1zsxMpTO1jSGlCP3jGYLNrjGzbywDaebGsujN3wEfJQ8VZYKYCdvgJ4jpl99sIZoVWD-t_uf8By0ao3k</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1924599413</pqid></control><display><type>article</type><title>Expression of ADAMTS13 in Normal and Abnormal Placentae and Its Potential Role in Angiogenesis and Placenta Development</title><source>MEDLINE</source><source>Alma/SFX Local Collection</source><source>Journals@Ovid Complete</source><creator>Xiao, Juan ; Feng, Yun ; Li, Xueyin ; Li, Wei ; Fan, Lei ; Liu, Jing ; Zeng, Xue ; Chen, Kaiyue ; Chen, Xi ; Zhou, Xiaoshui ; Zheng, X Long ; Chen, Suhua</creator><creatorcontrib>Xiao, Juan ; Feng, Yun ; Li, Xueyin ; Li, Wei ; Fan, Lei ; Liu, Jing ; Zeng, Xue ; Chen, Kaiyue ; Chen, Xi ; Zhou, Xiaoshui ; Zheng, X Long ; Chen, Suhua</creatorcontrib><description>OBJECTIVE—ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 repeats, member 13) is primarily synthesized in liver. The biosynthesis of ADAMTS13 and its physiological role in placenta are not known. APPROACH AND RESULTS—We used real-time polymerase chain reaction, immunohistochemistry, and Western blotting analyses, as well as proteolytic cleavage of FRETS (fluorescent resonance energy transfers)-VWF73, to determine ADAMTS13 expression in placenta and trophoblasts obtained from individuals with normal pregnancy and patients with severe preeclampsia. We also determined the role of ADAMTS13 in extravillous trophoblasts using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, wound scratch assay, transwell migration assay, tube formation assay, and tissue outgrowth assays. We showed that full-length and proteolytically active ADAMTS13 was expressed in normal human placenta, primarily in the trophoblasts and villous core fetal vessel endothelium during pregnancy. Placental expression of ADAMTS13 mRNA, protein, and proteolytic activity was at the highest levels during the first trimester and significantly reduced at the term of gestation. Additionally, significantly reduced levels of placental ADAMTS13 expression was detected under hypoxic conditions and in patients with preeclampsia. In addition, recombinant ADAMTS13 protease stimulated proliferation, migration, invasion, and network formation of trophoblastic cells in culture. Finally, knockdown of ADAMTS13 expression attenuated the ability of tube formation in trophoblast (HTR-8/SVNEO) cells and the extravillous trophoblast outgrowth in placental explants. CONCLUSIONS—Our results demonstrate for the first time the expression of ADAMTS13 mRNA and protein in normal and abnormal placental tissues and its role in promoting angiogenesis and trophoblastic cell development. The findings support the potential role of the ADAMTS13–von Willebrand factor pathway in normal pregnancy and pathogenesis of preeclampsia.</description><identifier>ISSN: 1079-5642</identifier><identifier>EISSN: 1524-4636</identifier><identifier>DOI: 10.1161/ATVBAHA.117.309735</identifier><identifier>PMID: 28751574</identifier><language>eng</language><publisher>United States: American Heart Association, Inc</publisher><subject>ADAMTS13 Protein - genetics ; ADAMTS13 Protein - metabolism ; Adult ; Animals ; Case-Control Studies ; Cell Movement ; Cell Proliferation ; CHO Cells ; Cricetulus ; Endothelial Cells - enzymology ; Female ; Gene Expression Regulation, Developmental ; Humans ; Neovascularization, Physiologic ; Placenta - blood supply ; Placenta - enzymology ; Placentation ; Pre-Eclampsia - enzymology ; Pre-Eclampsia - genetics ; Pre-Eclampsia - physiopathology ; Pregnancy ; Pregnancy Trimesters ; Proteolysis ; RNA Interference ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Signal Transduction ; Tissue Culture Techniques ; Transfection ; Trophoblasts - enzymology ; von Willebrand Factor - metabolism</subject><ispartof>Arteriosclerosis, thrombosis, and vascular biology, 2017-09, Vol.37 (9), p.1748-1756</ispartof><rights>2017 American Heart Association, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5155-ee118b191f8179d6d38286ed32b135719876dc594830c99bc885b3ae0439fc933</citedby><cites>FETCH-LOGICAL-c5155-ee118b191f8179d6d38286ed32b135719876dc594830c99bc885b3ae0439fc933</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28751574$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xiao, Juan</creatorcontrib><creatorcontrib>Feng, Yun</creatorcontrib><creatorcontrib>Li, Xueyin</creatorcontrib><creatorcontrib>Li, Wei</creatorcontrib><creatorcontrib>Fan, Lei</creatorcontrib><creatorcontrib>Liu, Jing</creatorcontrib><creatorcontrib>Zeng, Xue</creatorcontrib><creatorcontrib>Chen, Kaiyue</creatorcontrib><creatorcontrib>Chen, Xi</creatorcontrib><creatorcontrib>Zhou, Xiaoshui</creatorcontrib><creatorcontrib>Zheng, X Long</creatorcontrib><creatorcontrib>Chen, Suhua</creatorcontrib><title>Expression of ADAMTS13 in Normal and Abnormal Placentae and Its Potential Role in Angiogenesis and Placenta Development</title><title>Arteriosclerosis, thrombosis, and vascular biology</title><addtitle>Arterioscler Thromb Vasc Biol</addtitle><description>OBJECTIVE—ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 repeats, member 13) is primarily synthesized in liver. The biosynthesis of ADAMTS13 and its physiological role in placenta are not known. APPROACH AND RESULTS—We used real-time polymerase chain reaction, immunohistochemistry, and Western blotting analyses, as well as proteolytic cleavage of FRETS (fluorescent resonance energy transfers)-VWF73, to determine ADAMTS13 expression in placenta and trophoblasts obtained from individuals with normal pregnancy and patients with severe preeclampsia. We also determined the role of ADAMTS13 in extravillous trophoblasts using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, wound scratch assay, transwell migration assay, tube formation assay, and tissue outgrowth assays. We showed that full-length and proteolytically active ADAMTS13 was expressed in normal human placenta, primarily in the trophoblasts and villous core fetal vessel endothelium during pregnancy. Placental expression of ADAMTS13 mRNA, protein, and proteolytic activity was at the highest levels during the first trimester and significantly reduced at the term of gestation. Additionally, significantly reduced levels of placental ADAMTS13 expression was detected under hypoxic conditions and in patients with preeclampsia. In addition, recombinant ADAMTS13 protease stimulated proliferation, migration, invasion, and network formation of trophoblastic cells in culture. Finally, knockdown of ADAMTS13 expression attenuated the ability of tube formation in trophoblast (HTR-8/SVNEO) cells and the extravillous trophoblast outgrowth in placental explants. CONCLUSIONS—Our results demonstrate for the first time the expression of ADAMTS13 mRNA and protein in normal and abnormal placental tissues and its role in promoting angiogenesis and trophoblastic cell development. The findings support the potential role of the ADAMTS13–von Willebrand factor pathway in normal pregnancy and pathogenesis of preeclampsia.</description><subject>ADAMTS13 Protein - genetics</subject><subject>ADAMTS13 Protein - metabolism</subject><subject>Adult</subject><subject>Animals</subject><subject>Case-Control Studies</subject><subject>Cell Movement</subject><subject>Cell Proliferation</subject><subject>CHO Cells</subject><subject>Cricetulus</subject><subject>Endothelial Cells - enzymology</subject><subject>Female</subject><subject>Gene Expression Regulation, Developmental</subject><subject>Humans</subject><subject>Neovascularization, Physiologic</subject><subject>Placenta - blood supply</subject><subject>Placenta - enzymology</subject><subject>Placentation</subject><subject>Pre-Eclampsia - enzymology</subject><subject>Pre-Eclampsia - genetics</subject><subject>Pre-Eclampsia - physiopathology</subject><subject>Pregnancy</subject><subject>Pregnancy Trimesters</subject><subject>Proteolysis</subject><subject>RNA Interference</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Signal Transduction</subject><subject>Tissue Culture Techniques</subject><subject>Transfection</subject><subject>Trophoblasts - enzymology</subject><subject>von Willebrand Factor - metabolism</subject><issn>1079-5642</issn><issn>1524-4636</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UU1v1DAUtBCIlsIf4IBy5JLij_jrghTa0lYqUMHC1XKSl12DE2_tbLf8e7zNtoILJ3vem5k30iD0muBjQgR5Vy9-fKgv6gzkMcNaMv4EHRJOq7ISTDzNfyx1yUVFD9CLlH5ijCtK8XN0QJXkhMvqEG3P7tYRUnJhLEJf1Kf1p8U3wgo3Fp9DHKwv7NgVdTPO4NrbFsbJwv34ckrFdZjywOXd1-Bhp6vHpQtLGCG5dE97EBWncAs-rIcMXqJnvfUJXu3fI_T949ni5KK8-nJ-eVJflW0OyEsAQlRDNOkVkboTHVNUCegYbQjjkmglRddyXSmGW62bVineMAu4YrpvNWNH6P3su940A3S7HNF6s45usPG3CdaZfzejW5lluDWcSywqkg3e7g1iuNlAmszgUgve2xHCJhmiacW1zsxMpTO1jSGlCP3jGYLNrjGzbywDaebGsujN3wEfJQ8VZYKYCdvgJ4jpl99sIZoVWD-t_uf8By0ao3k</recordid><startdate>201709</startdate><enddate>201709</enddate><creator>Xiao, Juan</creator><creator>Feng, Yun</creator><creator>Li, Xueyin</creator><creator>Li, Wei</creator><creator>Fan, Lei</creator><creator>Liu, Jing</creator><creator>Zeng, Xue</creator><creator>Chen, Kaiyue</creator><creator>Chen, Xi</creator><creator>Zhou, Xiaoshui</creator><creator>Zheng, X Long</creator><creator>Chen, Suhua</creator><general>American Heart Association, Inc</general><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><scope>5PM</scope></search><sort><creationdate>201709</creationdate><title>Expression of ADAMTS13 in Normal and Abnormal Placentae and Its Potential Role in Angiogenesis and Placenta Development</title><author>Xiao, Juan ; Feng, Yun ; Li, Xueyin ; Li, Wei ; Fan, Lei ; Liu, Jing ; Zeng, Xue ; Chen, Kaiyue ; Chen, Xi ; Zhou, Xiaoshui ; Zheng, X Long ; Chen, Suhua</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5155-ee118b191f8179d6d38286ed32b135719876dc594830c99bc885b3ae0439fc933</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>ADAMTS13 Protein - genetics</topic><topic>ADAMTS13 Protein - metabolism</topic><topic>Adult</topic><topic>Animals</topic><topic>Case-Control Studies</topic><topic>Cell Movement</topic><topic>Cell Proliferation</topic><topic>CHO Cells</topic><topic>Cricetulus</topic><topic>Endothelial Cells - enzymology</topic><topic>Female</topic><topic>Gene Expression Regulation, Developmental</topic><topic>Humans</topic><topic>Neovascularization, Physiologic</topic><topic>Placenta - blood supply</topic><topic>Placenta - enzymology</topic><topic>Placentation</topic><topic>Pre-Eclampsia - enzymology</topic><topic>Pre-Eclampsia - genetics</topic><topic>Pre-Eclampsia - physiopathology</topic><topic>Pregnancy</topic><topic>Pregnancy Trimesters</topic><topic>Proteolysis</topic><topic>RNA Interference</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Signal Transduction</topic><topic>Tissue Culture Techniques</topic><topic>Transfection</topic><topic>Trophoblasts - enzymology</topic><topic>von Willebrand Factor - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xiao, Juan</creatorcontrib><creatorcontrib>Feng, Yun</creatorcontrib><creatorcontrib>Li, Xueyin</creatorcontrib><creatorcontrib>Li, Wei</creatorcontrib><creatorcontrib>Fan, Lei</creatorcontrib><creatorcontrib>Liu, Jing</creatorcontrib><creatorcontrib>Zeng, Xue</creatorcontrib><creatorcontrib>Chen, Kaiyue</creatorcontrib><creatorcontrib>Chen, Xi</creatorcontrib><creatorcontrib>Zhou, Xiaoshui</creatorcontrib><creatorcontrib>Zheng, X Long</creatorcontrib><creatorcontrib>Chen, Suhua</creatorcontrib><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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xiao, Juan</au><au>Feng, Yun</au><au>Li, Xueyin</au><au>Li, Wei</au><au>Fan, Lei</au><au>Liu, Jing</au><au>Zeng, Xue</au><au>Chen, Kaiyue</au><au>Chen, Xi</au><au>Zhou, Xiaoshui</au><au>Zheng, X Long</au><au>Chen, Suhua</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of ADAMTS13 in Normal and Abnormal Placentae and Its Potential Role in Angiogenesis and Placenta Development</atitle><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle><addtitle>Arterioscler Thromb Vasc Biol</addtitle><date>2017-09</date><risdate>2017</risdate><volume>37</volume><issue>9</issue><spage>1748</spage><epage>1756</epage><pages>1748-1756</pages><issn>1079-5642</issn><eissn>1524-4636</eissn><abstract>OBJECTIVE—ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 repeats, member 13) is primarily synthesized in liver. The biosynthesis of ADAMTS13 and its physiological role in placenta are not known. APPROACH AND RESULTS—We used real-time polymerase chain reaction, immunohistochemistry, and Western blotting analyses, as well as proteolytic cleavage of FRETS (fluorescent resonance energy transfers)-VWF73, to determine ADAMTS13 expression in placenta and trophoblasts obtained from individuals with normal pregnancy and patients with severe preeclampsia. We also determined the role of ADAMTS13 in extravillous trophoblasts using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, wound scratch assay, transwell migration assay, tube formation assay, and tissue outgrowth assays. We showed that full-length and proteolytically active ADAMTS13 was expressed in normal human placenta, primarily in the trophoblasts and villous core fetal vessel endothelium during pregnancy. Placental expression of ADAMTS13 mRNA, protein, and proteolytic activity was at the highest levels during the first trimester and significantly reduced at the term of gestation. Additionally, significantly reduced levels of placental ADAMTS13 expression was detected under hypoxic conditions and in patients with preeclampsia. In addition, recombinant ADAMTS13 protease stimulated proliferation, migration, invasion, and network formation of trophoblastic cells in culture. Finally, knockdown of ADAMTS13 expression attenuated the ability of tube formation in trophoblast (HTR-8/SVNEO) cells and the extravillous trophoblast outgrowth in placental explants. CONCLUSIONS—Our results demonstrate for the first time the expression of ADAMTS13 mRNA and protein in normal and abnormal placental tissues and its role in promoting angiogenesis and trophoblastic cell development. The findings support the potential role of the ADAMTS13–von Willebrand factor pathway in normal pregnancy and pathogenesis of preeclampsia.</abstract><cop>United States</cop><pub>American Heart Association, Inc</pub><pmid>28751574</pmid><doi>10.1161/ATVBAHA.117.309735</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1079-5642
ispartof Arteriosclerosis, thrombosis, and vascular biology, 2017-09, Vol.37 (9), p.1748-1756
issn 1079-5642
1524-4636
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5570641
source MEDLINE; Alma/SFX Local Collection; Journals@Ovid Complete
subjects ADAMTS13 Protein - genetics
ADAMTS13 Protein - metabolism
Adult
Animals
Case-Control Studies
Cell Movement
Cell Proliferation
CHO Cells
Cricetulus
Endothelial Cells - enzymology
Female
Gene Expression Regulation, Developmental
Humans
Neovascularization, Physiologic
Placenta - blood supply
Placenta - enzymology
Placentation
Pre-Eclampsia - enzymology
Pre-Eclampsia - genetics
Pre-Eclampsia - physiopathology
Pregnancy
Pregnancy Trimesters
Proteolysis
RNA Interference
RNA, Messenger - genetics
RNA, Messenger - metabolism
Signal Transduction
Tissue Culture Techniques
Transfection
Trophoblasts - enzymology
von Willebrand Factor - metabolism
title Expression of ADAMTS13 in Normal and Abnormal Placentae and Its Potential Role in Angiogenesis and Placenta Development
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-31T01%3A54%3A54IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Expression%20of%20ADAMTS13%20in%20Normal%20and%20Abnormal%20Placentae%20and%20Its%20Potential%20Role%20in%20Angiogenesis%20and%20Placenta%20Development&rft.jtitle=Arteriosclerosis,%20thrombosis,%20and%20vascular%20biology&rft.au=Xiao,%20Juan&rft.date=2017-09&rft.volume=37&rft.issue=9&rft.spage=1748&rft.epage=1756&rft.pages=1748-1756&rft.issn=1079-5642&rft.eissn=1524-4636&rft_id=info:doi/10.1161/ATVBAHA.117.309735&rft_dat=%3Cproquest_pubme%3E1924599413%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1924599413&rft_id=info:pmid/28751574&rfr_iscdi=true