BRG1 expression is increased in thoracic aortic aneurysms and regulates proliferation and apoptosis of vascular smooth muscle cells through the long non-coding RNA HIF1A-AS1 in vitro

OBJECTIVES Brahma-related gene 1 (BRG1) and long non-coding RNAs (lncRNAs) play important roles in cellular processes. However, little is known regarding their roles in thoracic aortic aneurysms. We investigated BRG1 expression in thoracic aortic aneurysms and the roles of BRG1 and the lncRNA HIF 1...

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Veröffentlicht in:European journal of cardio-thoracic surgery 2015-03, Vol.47 (3), p.439-446
Hauptverfasser: Wang, Shuwei, Zhang, Xiwu, Yuan, Yang, Tan, Mengwei, Zhang, Le, Xue, Xiang, Yan, Yan, Han, Lin, Xu, Zhiyun
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container_issue 3
container_start_page 439
container_title European journal of cardio-thoracic surgery
container_volume 47
creator Wang, Shuwei
Zhang, Xiwu
Yuan, Yang
Tan, Mengwei
Zhang, Le
Xue, Xiang
Yan, Yan
Han, Lin
Xu, Zhiyun
description OBJECTIVES Brahma-related gene 1 (BRG1) and long non-coding RNAs (lncRNAs) play important roles in cellular processes. However, little is known regarding their roles in thoracic aortic aneurysms. We investigated BRG1 expression in thoracic aortic aneurysms and the roles of BRG1 and the lncRNA HIF 1 alpha-antisense RNA 1 in regulating the proliferation and apoptosis of aortic smooth muscle cells in vitro. METHODS BRG1 mRNA and protein expression in human aortic media specimens were examined by quantitative real-time polymerase chain reaction, immunohistochemical staining and western blot. BRG1 expression was up-regulated by lentiviral vectors. Vascular smooth muscle cell proliferation and apoptosis were studied using Cell Counting Kit-8 and terminal deoxynucleotidyl transferase dUTP nick-end labelling assays. We performed western blots to detect Caspase3 and Bcl2 protein expression. LncRNAs regulated by BRG1 were identified through microarray in BRG1 gain- and loss-of-function vascular smooth muscle cells. Finally, the expression of HIF 1 alpha-antisense RNA 1 was reduced by siRNA and cell proliferation and apoptosis was studied using Cell Counting Kit-8 assays, caspase-3 activity assays and western blot. RESULTS BRG1 expression in the aortic media was significantly higher in thoracic aortic aneurysms than in normal controls. Overexpression of BRG1 in human aortic smooth muscle cells promoted apoptosis and reduced proliferation. The expression of HIF 1 alpha-antisense RNA 1 was significantly down- and up-regulated in BRG1 knock-down and overexpressing vascular smooth muscle cells, respectively. We further demonstrated that suppression of HIF 1 alpha-antisense RNA 1 by siRNA in vascular smooth muscle cells reduced apoptosis and promoted proliferation. CONCLUSIONS BRG1 is overexpressed in the aortic media of thoracic aortic aneurysms and the interaction between BRG1 and HIF 1 alpha-antisense RNA 1 plays a key role in the proliferation and apoptosis of vascular smooth muscle cells in vitro, which may contribute to the pathogenesis of thoracic aortic aneurysms.
doi_str_mv 10.1093/ejcts/ezu215
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However, little is known regarding their roles in thoracic aortic aneurysms. We investigated BRG1 expression in thoracic aortic aneurysms and the roles of BRG1 and the lncRNA HIF 1 alpha-antisense RNA 1 in regulating the proliferation and apoptosis of aortic smooth muscle cells in vitro. METHODS BRG1 mRNA and protein expression in human aortic media specimens were examined by quantitative real-time polymerase chain reaction, immunohistochemical staining and western blot. BRG1 expression was up-regulated by lentiviral vectors. Vascular smooth muscle cell proliferation and apoptosis were studied using Cell Counting Kit-8 and terminal deoxynucleotidyl transferase dUTP nick-end labelling assays. We performed western blots to detect Caspase3 and Bcl2 protein expression. LncRNAs regulated by BRG1 were identified through microarray in BRG1 gain- and loss-of-function vascular smooth muscle cells. Finally, the expression of HIF 1 alpha-antisense RNA 1 was reduced by siRNA and cell proliferation and apoptosis was studied using Cell Counting Kit-8 assays, caspase-3 activity assays and western blot. RESULTS BRG1 expression in the aortic media was significantly higher in thoracic aortic aneurysms than in normal controls. Overexpression of BRG1 in human aortic smooth muscle cells promoted apoptosis and reduced proliferation. The expression of HIF 1 alpha-antisense RNA 1 was significantly down- and up-regulated in BRG1 knock-down and overexpressing vascular smooth muscle cells, respectively. We further demonstrated that suppression of HIF 1 alpha-antisense RNA 1 by siRNA in vascular smooth muscle cells reduced apoptosis and promoted proliferation. CONCLUSIONS BRG1 is overexpressed in the aortic media of thoracic aortic aneurysms and the interaction between BRG1 and HIF 1 alpha-antisense RNA 1 plays a key role in the proliferation and apoptosis of vascular smooth muscle cells in vitro, which may contribute to the pathogenesis of thoracic aortic aneurysms.</description><identifier>ISSN: 1010-7940</identifier><identifier>EISSN: 1873-734X</identifier><identifier>DOI: 10.1093/ejcts/ezu215</identifier><identifier>PMID: 24875884</identifier><language>eng</language><publisher>Germany: Oxford University Press</publisher><subject>Aorta, Thoracic - chemistry ; Aorta, Thoracic - metabolism ; Aortic Aneurysm, Thoracic - metabolism ; Apoptosis - genetics ; Cell Line ; Cell Proliferation - genetics ; DNA Helicases - analysis ; DNA Helicases - genetics ; DNA Helicases - metabolism ; Gene Silencing ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit - genetics ; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism ; Muscle, Smooth, Vascular - cytology ; Muscle, Smooth, Vascular - metabolism ; Nuclear Proteins - analysis ; Nuclear Proteins - genetics ; Nuclear Proteins - metabolism ; RNA, Long Noncoding - metabolism ; Transcription Factors - analysis ; Transcription Factors - genetics ; Transcription Factors - metabolism</subject><ispartof>European journal of cardio-thoracic surgery, 2015-03, Vol.47 (3), p.439-446</ispartof><rights>The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. 2014</rights><rights>The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c427t-18de2744254d28cca8a70cdd065cb9dcd2376d3edd4f0290d22567817098f2693</citedby><cites>FETCH-LOGICAL-c427t-18de2744254d28cca8a70cdd065cb9dcd2376d3edd4f0290d22567817098f2693</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1578,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24875884$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Shuwei</creatorcontrib><creatorcontrib>Zhang, Xiwu</creatorcontrib><creatorcontrib>Yuan, Yang</creatorcontrib><creatorcontrib>Tan, Mengwei</creatorcontrib><creatorcontrib>Zhang, Le</creatorcontrib><creatorcontrib>Xue, Xiang</creatorcontrib><creatorcontrib>Yan, Yan</creatorcontrib><creatorcontrib>Han, Lin</creatorcontrib><creatorcontrib>Xu, Zhiyun</creatorcontrib><title>BRG1 expression is increased in thoracic aortic aneurysms and regulates proliferation and apoptosis of vascular smooth muscle cells through the long non-coding RNA HIF1A-AS1 in vitro</title><title>European journal of cardio-thoracic surgery</title><addtitle>Eur J Cardiothorac Surg</addtitle><description>OBJECTIVES Brahma-related gene 1 (BRG1) and long non-coding RNAs (lncRNAs) play important roles in cellular processes. However, little is known regarding their roles in thoracic aortic aneurysms. We investigated BRG1 expression in thoracic aortic aneurysms and the roles of BRG1 and the lncRNA HIF 1 alpha-antisense RNA 1 in regulating the proliferation and apoptosis of aortic smooth muscle cells in vitro. METHODS BRG1 mRNA and protein expression in human aortic media specimens were examined by quantitative real-time polymerase chain reaction, immunohistochemical staining and western blot. BRG1 expression was up-regulated by lentiviral vectors. Vascular smooth muscle cell proliferation and apoptosis were studied using Cell Counting Kit-8 and terminal deoxynucleotidyl transferase dUTP nick-end labelling assays. We performed western blots to detect Caspase3 and Bcl2 protein expression. LncRNAs regulated by BRG1 were identified through microarray in BRG1 gain- and loss-of-function vascular smooth muscle cells. Finally, the expression of HIF 1 alpha-antisense RNA 1 was reduced by siRNA and cell proliferation and apoptosis was studied using Cell Counting Kit-8 assays, caspase-3 activity assays and western blot. RESULTS BRG1 expression in the aortic media was significantly higher in thoracic aortic aneurysms than in normal controls. Overexpression of BRG1 in human aortic smooth muscle cells promoted apoptosis and reduced proliferation. The expression of HIF 1 alpha-antisense RNA 1 was significantly down- and up-regulated in BRG1 knock-down and overexpressing vascular smooth muscle cells, respectively. We further demonstrated that suppression of HIF 1 alpha-antisense RNA 1 by siRNA in vascular smooth muscle cells reduced apoptosis and promoted proliferation. CONCLUSIONS BRG1 is overexpressed in the aortic media of thoracic aortic aneurysms and the interaction between BRG1 and HIF 1 alpha-antisense RNA 1 plays a key role in the proliferation and apoptosis of vascular smooth muscle cells in vitro, which may contribute to the pathogenesis of thoracic aortic aneurysms.</description><subject>Aorta, Thoracic - chemistry</subject><subject>Aorta, Thoracic - metabolism</subject><subject>Aortic Aneurysm, Thoracic - metabolism</subject><subject>Apoptosis - genetics</subject><subject>Cell Line</subject><subject>Cell Proliferation - genetics</subject><subject>DNA Helicases - analysis</subject><subject>DNA Helicases - genetics</subject><subject>DNA Helicases - metabolism</subject><subject>Gene Silencing</subject><subject>Humans</subject><subject>Hypoxia-Inducible Factor 1, alpha Subunit - genetics</subject><subject>Hypoxia-Inducible Factor 1, alpha Subunit - metabolism</subject><subject>Muscle, Smooth, Vascular - cytology</subject><subject>Muscle, Smooth, Vascular - metabolism</subject><subject>Nuclear Proteins - analysis</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - metabolism</subject><subject>RNA, Long Noncoding - metabolism</subject><subject>Transcription Factors - analysis</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><issn>1010-7940</issn><issn>1873-734X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU9vFSEUxYnR2FrduTbsdOFYYJiBWT4b-ydpNKmauJtQuPMezcwwcqGxfjA_X5m-6tLVOQk_DvdyCHnN2QfOuvoYbmzCY_idBW-ekEOuVV2pWv54WjzjrFKdZAfkBeINY6ythXpODoTUqtFaHpI_H6_OOIVfSwREH2bqkfrZRjAIrjiadiEa6y01IaZVZsjxDicsztEI2zyaBEiXGEY_QDRpTVnPzBKWFLAEhoHeGrSFjBSnENKOThntCNTCOGJ5I4a83RUFOoZ5S-cwVzY4X-zV5w09vzjlm2rzla8D3foUw0vybDAjwqtHPSLfTz99OzmvLr-cXZxsLisrhUoV1w6EklI00gltrdFGMescaxt73TnrRK1aV4NzcmCiY06IplWaK9bpQbRdfUTe7XPLej8zYOonj-vQ5RtCxp63TVOu1JwX9P0etTEgRhj6JfrJxLues35tqn9oqt83VfA3j8n5egL3D_5bTQHe7oGQl_9H3QP3_aFH</recordid><startdate>20150301</startdate><enddate>20150301</enddate><creator>Wang, Shuwei</creator><creator>Zhang, Xiwu</creator><creator>Yuan, Yang</creator><creator>Tan, Mengwei</creator><creator>Zhang, Le</creator><creator>Xue, Xiang</creator><creator>Yan, Yan</creator><creator>Han, Lin</creator><creator>Xu, Zhiyun</creator><general>Oxford University Press</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></search><sort><creationdate>20150301</creationdate><title>BRG1 expression is increased in thoracic aortic aneurysms and regulates proliferation and apoptosis of vascular smooth muscle cells through the long non-coding RNA HIF1A-AS1 in vitro</title><author>Wang, Shuwei ; Zhang, Xiwu ; Yuan, Yang ; Tan, Mengwei ; Zhang, Le ; Xue, Xiang ; Yan, Yan ; Han, Lin ; Xu, Zhiyun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c427t-18de2744254d28cca8a70cdd065cb9dcd2376d3edd4f0290d22567817098f2693</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Aorta, Thoracic - chemistry</topic><topic>Aorta, Thoracic - metabolism</topic><topic>Aortic Aneurysm, Thoracic - metabolism</topic><topic>Apoptosis - genetics</topic><topic>Cell Line</topic><topic>Cell Proliferation - genetics</topic><topic>DNA Helicases - analysis</topic><topic>DNA Helicases - genetics</topic><topic>DNA Helicases - metabolism</topic><topic>Gene Silencing</topic><topic>Humans</topic><topic>Hypoxia-Inducible Factor 1, alpha Subunit - genetics</topic><topic>Hypoxia-Inducible Factor 1, alpha Subunit - metabolism</topic><topic>Muscle, Smooth, Vascular - cytology</topic><topic>Muscle, Smooth, Vascular - metabolism</topic><topic>Nuclear Proteins - analysis</topic><topic>Nuclear Proteins - genetics</topic><topic>Nuclear Proteins - metabolism</topic><topic>RNA, Long Noncoding - metabolism</topic><topic>Transcription Factors - analysis</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Shuwei</creatorcontrib><creatorcontrib>Zhang, Xiwu</creatorcontrib><creatorcontrib>Yuan, Yang</creatorcontrib><creatorcontrib>Tan, Mengwei</creatorcontrib><creatorcontrib>Zhang, Le</creatorcontrib><creatorcontrib>Xue, Xiang</creatorcontrib><creatorcontrib>Yan, Yan</creatorcontrib><creatorcontrib>Han, Lin</creatorcontrib><creatorcontrib>Xu, Zhiyun</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><jtitle>European journal of cardio-thoracic surgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Shuwei</au><au>Zhang, Xiwu</au><au>Yuan, Yang</au><au>Tan, Mengwei</au><au>Zhang, Le</au><au>Xue, Xiang</au><au>Yan, Yan</au><au>Han, Lin</au><au>Xu, Zhiyun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>BRG1 expression is increased in thoracic aortic aneurysms and regulates proliferation and apoptosis of vascular smooth muscle cells through the long non-coding RNA HIF1A-AS1 in vitro</atitle><jtitle>European journal of cardio-thoracic surgery</jtitle><addtitle>Eur J Cardiothorac Surg</addtitle><date>2015-03-01</date><risdate>2015</risdate><volume>47</volume><issue>3</issue><spage>439</spage><epage>446</epage><pages>439-446</pages><issn>1010-7940</issn><eissn>1873-734X</eissn><abstract>OBJECTIVES Brahma-related gene 1 (BRG1) and long non-coding RNAs (lncRNAs) play important roles in cellular processes. However, little is known regarding their roles in thoracic aortic aneurysms. We investigated BRG1 expression in thoracic aortic aneurysms and the roles of BRG1 and the lncRNA HIF 1 alpha-antisense RNA 1 in regulating the proliferation and apoptosis of aortic smooth muscle cells in vitro. METHODS BRG1 mRNA and protein expression in human aortic media specimens were examined by quantitative real-time polymerase chain reaction, immunohistochemical staining and western blot. BRG1 expression was up-regulated by lentiviral vectors. Vascular smooth muscle cell proliferation and apoptosis were studied using Cell Counting Kit-8 and terminal deoxynucleotidyl transferase dUTP nick-end labelling assays. We performed western blots to detect Caspase3 and Bcl2 protein expression. LncRNAs regulated by BRG1 were identified through microarray in BRG1 gain- and loss-of-function vascular smooth muscle cells. Finally, the expression of HIF 1 alpha-antisense RNA 1 was reduced by siRNA and cell proliferation and apoptosis was studied using Cell Counting Kit-8 assays, caspase-3 activity assays and western blot. RESULTS BRG1 expression in the aortic media was significantly higher in thoracic aortic aneurysms than in normal controls. Overexpression of BRG1 in human aortic smooth muscle cells promoted apoptosis and reduced proliferation. The expression of HIF 1 alpha-antisense RNA 1 was significantly down- and up-regulated in BRG1 knock-down and overexpressing vascular smooth muscle cells, respectively. We further demonstrated that suppression of HIF 1 alpha-antisense RNA 1 by siRNA in vascular smooth muscle cells reduced apoptosis and promoted proliferation. CONCLUSIONS BRG1 is overexpressed in the aortic media of thoracic aortic aneurysms and the interaction between BRG1 and HIF 1 alpha-antisense RNA 1 plays a key role in the proliferation and apoptosis of vascular smooth muscle cells in vitro, which may contribute to the pathogenesis of thoracic aortic aneurysms.</abstract><cop>Germany</cop><pub>Oxford University Press</pub><pmid>24875884</pmid><doi>10.1093/ejcts/ezu215</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
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subjects Aorta, Thoracic - chemistry
Aorta, Thoracic - metabolism
Aortic Aneurysm, Thoracic - metabolism
Apoptosis - genetics
Cell Line
Cell Proliferation - genetics
DNA Helicases - analysis
DNA Helicases - genetics
DNA Helicases - metabolism
Gene Silencing
Humans
Hypoxia-Inducible Factor 1, alpha Subunit - genetics
Hypoxia-Inducible Factor 1, alpha Subunit - metabolism
Muscle, Smooth, Vascular - cytology
Muscle, Smooth, Vascular - metabolism
Nuclear Proteins - analysis
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
RNA, Long Noncoding - metabolism
Transcription Factors - analysis
Transcription Factors - genetics
Transcription Factors - metabolism
title BRG1 expression is increased in thoracic aortic aneurysms and regulates proliferation and apoptosis of vascular smooth muscle cells through the long non-coding RNA HIF1A-AS1 in vitro
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