Aging differentially modulates the Wnt pro‐survival signalling pathways in vascular smooth muscle cells
We previously reported pro‐survival effects of Wnt3a and Wnt5a proteins in vascular smooth muscle cells (VSMCs). Wnt5a achieved this through induction of Wnt1‐inducible signalling pathway protein‐1 (WISP‐1) consequent to β‐catenin/CREB‐dependent, TCF‐independent, signalling. However, we found that a...
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| Veröffentlicht in: | Aging cell 2019-02, Vol.18 (1), p.e12844-n/a |
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| creator | Brown, Bethan A. Connolly, Georgia M. Mill, Carina E. J. Williams, Helen Angelini, Gianni D. Johnson, Jason L. George, Sarah J. |
| description | We previously reported pro‐survival effects of Wnt3a and Wnt5a proteins in vascular smooth muscle cells (VSMCs). Wnt5a achieved this through induction of Wnt1‐inducible signalling pathway protein‐1 (WISP‐1) consequent to β‐catenin/CREB‐dependent, TCF‐independent, signalling. However, we found that as atherosclerosis advances, although Wnt5a protein was increased, WISP‐1 was reduced. We hypothesized this disconnect could be due to aging. In this study, we elucidate the mechanism underlying Wnt3a pro‐survival signalling and demonstrate the differential effect of age on Wnt3a‐ and Wnt5a‐mediated survival. We show Wnt3a protein was expressed in human atherosclerotic coronary arteries and co‐located with macrophages and VSMCs. Meanwhile, Wnt3a stimulation of primary mouse VSMCs increased β‐catenin nuclear translocation and TCF, but not CREB, activation. Wnt3a increased mRNA expression of the pro‐survival factor WISP‐2 in a TCF‐dependent manner. Functionally, β‐catenin/TCF inhibition or WISP‐2 neutralization significantly impaired Wnt3a‐mediated VSMC survival. WISP‐2 was upregulated in human atherosclerosis and partly co‐localized with Wnt3a. The pro‐survival action of Wnt3a was effective in VSMCs from young (2 month) and old (18–20 month) mice, whereas Wnt5a‐mediated rescue was impaired with age. Further investigation revealed that although Wnt5a induced β‐catenin nuclear translocation in VSMCs from both ages, CREB phosphorylation and WISP‐1 upregulation did not occur in old VSMCs. Unlike Wnt5a, pro‐survival Wnt3a signalling involves β‐catenin/TCF and WISP‐2. While Wnt3a‐mediated survival was unchanged with age, Wnt5a‐mediated survival was lost due to impaired CREB activation and WISP‐1 regulation. Greater understanding of the effect of age on Wnt signalling may identify targets to promote VSMC survival in elderly patients with atherosclerosis. |
| doi_str_mv | 10.1111/acel.12844 |
| format | Article |
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J. ; Williams, Helen ; Angelini, Gianni D. ; Johnson, Jason L. ; George, Sarah J.</creator><creatorcontrib>Brown, Bethan A. ; Connolly, Georgia M. ; Mill, Carina E. J. ; Williams, Helen ; Angelini, Gianni D. ; Johnson, Jason L. ; George, Sarah J.</creatorcontrib><description>We previously reported pro‐survival effects of Wnt3a and Wnt5a proteins in vascular smooth muscle cells (VSMCs). Wnt5a achieved this through induction of Wnt1‐inducible signalling pathway protein‐1 (WISP‐1) consequent to β‐catenin/CREB‐dependent, TCF‐independent, signalling. However, we found that as atherosclerosis advances, although Wnt5a protein was increased, WISP‐1 was reduced. We hypothesized this disconnect could be due to aging. In this study, we elucidate the mechanism underlying Wnt3a pro‐survival signalling and demonstrate the differential effect of age on Wnt3a‐ and Wnt5a‐mediated survival. We show Wnt3a protein was expressed in human atherosclerotic coronary arteries and co‐located with macrophages and VSMCs. Meanwhile, Wnt3a stimulation of primary mouse VSMCs increased β‐catenin nuclear translocation and TCF, but not CREB, activation. Wnt3a increased mRNA expression of the pro‐survival factor WISP‐2 in a TCF‐dependent manner. Functionally, β‐catenin/TCF inhibition or WISP‐2 neutralization significantly impaired Wnt3a‐mediated VSMC survival. WISP‐2 was upregulated in human atherosclerosis and partly co‐localized with Wnt3a. The pro‐survival action of Wnt3a was effective in VSMCs from young (2 month) and old (18–20 month) mice, whereas Wnt5a‐mediated rescue was impaired with age. Further investigation revealed that although Wnt5a induced β‐catenin nuclear translocation in VSMCs from both ages, CREB phosphorylation and WISP‐1 upregulation did not occur in old VSMCs. Unlike Wnt5a, pro‐survival Wnt3a signalling involves β‐catenin/TCF and WISP‐2. While Wnt3a‐mediated survival was unchanged with age, Wnt5a‐mediated survival was lost due to impaired CREB activation and WISP‐1 regulation. Greater understanding of the effect of age on Wnt signalling may identify targets to promote VSMC survival in elderly patients with atherosclerosis.</description><identifier>ISSN: 1474-9718</identifier><identifier>EISSN: 1474-9726</identifier><identifier>DOI: 10.1111/acel.12844</identifier><identifier>PMID: 30548452</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Adolescent ; Adult ; Age ; Aging ; Animals ; apoptosis ; Apoptosis - drug effects ; Arteriosclerosis ; Atherosclerosis ; Atherosclerosis - metabolism ; Atherosclerosis - pathology ; beta Catenin - metabolism ; Catenin ; CCN Intercellular Signaling Proteins - metabolism ; Cell Survival - drug effects ; Cellular Senescence - drug effects ; Child ; Coronary artery ; Cyclic AMP response element-binding protein ; Cyclic AMP Response Element-Binding Protein - metabolism ; Frizzled Receptors - metabolism ; Gene expression ; Gene Expression Regulation - drug effects ; Geriatrics ; Humans ; Hydrogen Peroxide - toxicity ; Macrophages ; Mice, Inbred C57BL ; Middle Aged ; Models, Biological ; Muscle, Smooth, Vascular - cytology ; Myocytes, Smooth Muscle - cytology ; Myocytes, Smooth Muscle - drug effects ; Myocytes, Smooth Muscle - metabolism ; Nuclear transport ; Original Paper ; Original Papers ; oxidative stress ; Phosphorylation ; Protein Binding - drug effects ; Proteins ; Repressor Proteins - metabolism ; RNA ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Signal transduction ; Smooth muscle ; Survival factor ; TCF Transcription Factors - metabolism ; Up-Regulation - drug effects ; vascular smooth muscle cell ; Wnt ; Wnt protein ; Wnt Signaling Pathway - drug effects ; Wnt-5a Protein - metabolism ; Wnt3A Protein - metabolism ; Young Adult</subject><ispartof>Aging cell, 2019-02, Vol.18 (1), p.e12844-n/a</ispartof><rights>2018 The Authors. published by the Anatomical Society and John Wiley & Sons Ltd.</rights><rights>2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.</rights><rights>COPYRIGHT 2018 John Wiley & Sons, Inc.</rights><rights>2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5154-10bf17d43f3db256a3e3b26e661470e65c5e334843476c27f5d4a12001abbf93</citedby><cites>FETCH-LOGICAL-c5154-10bf17d43f3db256a3e3b26e661470e65c5e334843476c27f5d4a12001abbf93</cites><orcidid>0000-0002-1426-8257</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351844/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351844/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,729,782,786,866,887,1419,11571,27933,27934,45583,45584,46061,46485,53800,53802</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30548452$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Brown, Bethan A.</creatorcontrib><creatorcontrib>Connolly, Georgia M.</creatorcontrib><creatorcontrib>Mill, Carina E. J.</creatorcontrib><creatorcontrib>Williams, Helen</creatorcontrib><creatorcontrib>Angelini, Gianni D.</creatorcontrib><creatorcontrib>Johnson, Jason L.</creatorcontrib><creatorcontrib>George, Sarah J.</creatorcontrib><title>Aging differentially modulates the Wnt pro‐survival signalling pathways in vascular smooth muscle cells</title><title>Aging cell</title><addtitle>Aging Cell</addtitle><description>We previously reported pro‐survival effects of Wnt3a and Wnt5a proteins in vascular smooth muscle cells (VSMCs). Wnt5a achieved this through induction of Wnt1‐inducible signalling pathway protein‐1 (WISP‐1) consequent to β‐catenin/CREB‐dependent, TCF‐independent, signalling. However, we found that as atherosclerosis advances, although Wnt5a protein was increased, WISP‐1 was reduced. We hypothesized this disconnect could be due to aging. In this study, we elucidate the mechanism underlying Wnt3a pro‐survival signalling and demonstrate the differential effect of age on Wnt3a‐ and Wnt5a‐mediated survival. We show Wnt3a protein was expressed in human atherosclerotic coronary arteries and co‐located with macrophages and VSMCs. Meanwhile, Wnt3a stimulation of primary mouse VSMCs increased β‐catenin nuclear translocation and TCF, but not CREB, activation. Wnt3a increased mRNA expression of the pro‐survival factor WISP‐2 in a TCF‐dependent manner. Functionally, β‐catenin/TCF inhibition or WISP‐2 neutralization significantly impaired Wnt3a‐mediated VSMC survival. WISP‐2 was upregulated in human atherosclerosis and partly co‐localized with Wnt3a. The pro‐survival action of Wnt3a was effective in VSMCs from young (2 month) and old (18–20 month) mice, whereas Wnt5a‐mediated rescue was impaired with age. Further investigation revealed that although Wnt5a induced β‐catenin nuclear translocation in VSMCs from both ages, CREB phosphorylation and WISP‐1 upregulation did not occur in old VSMCs. Unlike Wnt5a, pro‐survival Wnt3a signalling involves β‐catenin/TCF and WISP‐2. While Wnt3a‐mediated survival was unchanged with age, Wnt5a‐mediated survival was lost due to impaired CREB activation and WISP‐1 regulation. Greater understanding of the effect of age on Wnt signalling may identify targets to promote VSMC survival in elderly patients with atherosclerosis.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Age</subject><subject>Aging</subject><subject>Animals</subject><subject>apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Arteriosclerosis</subject><subject>Atherosclerosis</subject><subject>Atherosclerosis - metabolism</subject><subject>Atherosclerosis - pathology</subject><subject>beta Catenin - metabolism</subject><subject>Catenin</subject><subject>CCN Intercellular Signaling Proteins - metabolism</subject><subject>Cell Survival - drug effects</subject><subject>Cellular Senescence - drug effects</subject><subject>Child</subject><subject>Coronary artery</subject><subject>Cyclic AMP response element-binding protein</subject><subject>Cyclic AMP Response Element-Binding Protein - metabolism</subject><subject>Frizzled Receptors - metabolism</subject><subject>Gene expression</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Geriatrics</subject><subject>Humans</subject><subject>Hydrogen Peroxide - toxicity</subject><subject>Macrophages</subject><subject>Mice, Inbred C57BL</subject><subject>Middle Aged</subject><subject>Models, Biological</subject><subject>Muscle, Smooth, Vascular - cytology</subject><subject>Myocytes, Smooth Muscle - cytology</subject><subject>Myocytes, Smooth Muscle - drug effects</subject><subject>Myocytes, Smooth Muscle - metabolism</subject><subject>Nuclear transport</subject><subject>Original Paper</subject><subject>Original Papers</subject><subject>oxidative stress</subject><subject>Phosphorylation</subject><subject>Protein Binding - drug effects</subject><subject>Proteins</subject><subject>Repressor Proteins - metabolism</subject><subject>RNA</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Signal transduction</subject><subject>Smooth muscle</subject><subject>Survival factor</subject><subject>TCF Transcription Factors - metabolism</subject><subject>Up-Regulation - drug effects</subject><subject>vascular smooth muscle cell</subject><subject>Wnt</subject><subject>Wnt protein</subject><subject>Wnt Signaling Pathway - drug effects</subject><subject>Wnt-5a Protein - metabolism</subject><subject>Wnt3A Protein - metabolism</subject><subject>Young Adult</subject><issn>1474-9718</issn><issn>1474-9726</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kc1qGzEUhUVpadKkmz5AEXRXsKvf0XhTMCb9AUM3gSyFRiONFTQjV5px8K6P0Gfsk_S6Tp0ESqWFhPSdo3t0EXpDyZzC-GCsi3PKaiGeoXMqlJgtFKuen_a0PkOvSrklhKoF4S_RGSdS1EKycxSWXRg63AbvXXbDGEyMe9yndopmdAWPG4dvhhFvc_r142eZ8i7sTMQldAOQB-nWjJs7sy84DHhnigVhxqVPadzgfio2Ogz1xXKJXngTi3t9v16g609X16svs_W3z19Xy_XMSirFjJLGU9UK7nnbMFkZ7njDKldVkIa4SlrpOIfquVCVZcrLVhjKIJtpGr_gF-jj0XY7Nb1rLWTKJuptDr3Je51M0E9vhrDRXdrpiksKXwgG7-4Ncvo-uTLq2zRlSFs0o4rJuiJMPVCdiU6HwScws30oVi8VUbUUC8mBmv-Dgtm6Ptg0OB_g_Ing_VFgcyolO38qnBJ9aLY-NFv_aTbAbx9HPaF_uwsAPQJ38Mz-P1Z6ubpaH01_A7zatj4</recordid><startdate>201902</startdate><enddate>201902</enddate><creator>Brown, Bethan A.</creator><creator>Connolly, Georgia M.</creator><creator>Mill, Carina E. J.</creator><creator>Williams, Helen</creator><creator>Angelini, Gianni D.</creator><creator>Johnson, Jason L.</creator><creator>George, Sarah J.</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</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>7QP</scope><scope>7TK</scope><scope>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1426-8257</orcidid></search><sort><creationdate>201902</creationdate><title>Aging differentially modulates the Wnt pro‐survival signalling pathways in vascular smooth muscle cells</title><author>Brown, Bethan A. ; Connolly, Georgia M. ; Mill, Carina E. J. ; Williams, Helen ; Angelini, Gianni D. ; Johnson, Jason L. ; George, Sarah J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5154-10bf17d43f3db256a3e3b26e661470e65c5e334843476c27f5d4a12001abbf93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Age</topic><topic>Aging</topic><topic>Animals</topic><topic>apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Arteriosclerosis</topic><topic>Atherosclerosis</topic><topic>Atherosclerosis - metabolism</topic><topic>Atherosclerosis - pathology</topic><topic>beta Catenin - metabolism</topic><topic>Catenin</topic><topic>CCN Intercellular Signaling Proteins - metabolism</topic><topic>Cell Survival - drug effects</topic><topic>Cellular Senescence - drug effects</topic><topic>Child</topic><topic>Coronary artery</topic><topic>Cyclic AMP response element-binding protein</topic><topic>Cyclic AMP Response Element-Binding Protein - metabolism</topic><topic>Frizzled Receptors - metabolism</topic><topic>Gene expression</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Geriatrics</topic><topic>Humans</topic><topic>Hydrogen Peroxide - toxicity</topic><topic>Macrophages</topic><topic>Mice, Inbred C57BL</topic><topic>Middle Aged</topic><topic>Models, Biological</topic><topic>Muscle, Smooth, Vascular - cytology</topic><topic>Myocytes, Smooth Muscle - cytology</topic><topic>Myocytes, Smooth Muscle - drug effects</topic><topic>Myocytes, Smooth Muscle - metabolism</topic><topic>Nuclear transport</topic><topic>Original Paper</topic><topic>Original Papers</topic><topic>oxidative stress</topic><topic>Phosphorylation</topic><topic>Protein Binding - drug effects</topic><topic>Proteins</topic><topic>Repressor Proteins - metabolism</topic><topic>RNA</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Signal transduction</topic><topic>Smooth muscle</topic><topic>Survival factor</topic><topic>TCF Transcription Factors - metabolism</topic><topic>Up-Regulation - drug effects</topic><topic>vascular smooth muscle cell</topic><topic>Wnt</topic><topic>Wnt protein</topic><topic>Wnt Signaling Pathway - drug effects</topic><topic>Wnt-5a Protein - metabolism</topic><topic>Wnt3A Protein - metabolism</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Brown, Bethan A.</creatorcontrib><creatorcontrib>Connolly, Georgia M.</creatorcontrib><creatorcontrib>Mill, Carina E. J.</creatorcontrib><creatorcontrib>Williams, Helen</creatorcontrib><creatorcontrib>Angelini, Gianni D.</creatorcontrib><creatorcontrib>Johnson, Jason L.</creatorcontrib><creatorcontrib>George, Sarah J.</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Wiley Online Library (Open Access Collection)</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Biological Science Database</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Aging cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Brown, Bethan A.</au><au>Connolly, Georgia M.</au><au>Mill, Carina E. J.</au><au>Williams, Helen</au><au>Angelini, Gianni D.</au><au>Johnson, Jason L.</au><au>George, Sarah J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Aging differentially modulates the Wnt pro‐survival signalling pathways in vascular smooth muscle cells</atitle><jtitle>Aging cell</jtitle><addtitle>Aging Cell</addtitle><date>2019-02</date><risdate>2019</risdate><volume>18</volume><issue>1</issue><spage>e12844</spage><epage>n/a</epage><pages>e12844-n/a</pages><issn>1474-9718</issn><eissn>1474-9726</eissn><abstract>We previously reported pro‐survival effects of Wnt3a and Wnt5a proteins in vascular smooth muscle cells (VSMCs). Wnt5a achieved this through induction of Wnt1‐inducible signalling pathway protein‐1 (WISP‐1) consequent to β‐catenin/CREB‐dependent, TCF‐independent, signalling. However, we found that as atherosclerosis advances, although Wnt5a protein was increased, WISP‐1 was reduced. We hypothesized this disconnect could be due to aging. In this study, we elucidate the mechanism underlying Wnt3a pro‐survival signalling and demonstrate the differential effect of age on Wnt3a‐ and Wnt5a‐mediated survival. We show Wnt3a protein was expressed in human atherosclerotic coronary arteries and co‐located with macrophages and VSMCs. Meanwhile, Wnt3a stimulation of primary mouse VSMCs increased β‐catenin nuclear translocation and TCF, but not CREB, activation. Wnt3a increased mRNA expression of the pro‐survival factor WISP‐2 in a TCF‐dependent manner. Functionally, β‐catenin/TCF inhibition or WISP‐2 neutralization significantly impaired Wnt3a‐mediated VSMC survival. WISP‐2 was upregulated in human atherosclerosis and partly co‐localized with Wnt3a. The pro‐survival action of Wnt3a was effective in VSMCs from young (2 month) and old (18–20 month) mice, whereas Wnt5a‐mediated rescue was impaired with age. Further investigation revealed that although Wnt5a induced β‐catenin nuclear translocation in VSMCs from both ages, CREB phosphorylation and WISP‐1 upregulation did not occur in old VSMCs. Unlike Wnt5a, pro‐survival Wnt3a signalling involves β‐catenin/TCF and WISP‐2. While Wnt3a‐mediated survival was unchanged with age, Wnt5a‐mediated survival was lost due to impaired CREB activation and WISP‐1 regulation. Greater understanding of the effect of age on Wnt signalling may identify targets to promote VSMC survival in elderly patients with atherosclerosis.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>30548452</pmid><doi>10.1111/acel.12844</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0002-1426-8257</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Adult Age Aging Animals apoptosis Apoptosis - drug effects Arteriosclerosis Atherosclerosis Atherosclerosis - metabolism Atherosclerosis - pathology beta Catenin - metabolism Catenin CCN Intercellular Signaling Proteins - metabolism Cell Survival - drug effects Cellular Senescence - drug effects Child Coronary artery Cyclic AMP response element-binding protein Cyclic AMP Response Element-Binding Protein - metabolism Frizzled Receptors - metabolism Gene expression Gene Expression Regulation - drug effects Geriatrics Humans Hydrogen Peroxide - toxicity Macrophages Mice, Inbred C57BL Middle Aged Models, Biological Muscle, Smooth, Vascular - cytology Myocytes, Smooth Muscle - cytology Myocytes, Smooth Muscle - drug effects Myocytes, Smooth Muscle - metabolism Nuclear transport Original Paper Original Papers oxidative stress Phosphorylation Protein Binding - drug effects Proteins Repressor Proteins - metabolism RNA RNA, Messenger - genetics RNA, Messenger - metabolism Signal transduction Smooth muscle Survival factor TCF Transcription Factors - metabolism Up-Regulation - drug effects vascular smooth muscle cell Wnt Wnt protein Wnt Signaling Pathway - drug effects Wnt-5a Protein - metabolism Wnt3A Protein - metabolism Young Adult |
| title | Aging differentially modulates the Wnt pro‐survival signalling pathways in vascular smooth muscle cells |
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