Increased monocyte adhesion by endothelial expression of VCAM-1 missense variation in vitro
Abstract Objective In whole genome and single gene analyses, genetic variation at the vascular cell adhesion molecule-1 ( VCAM-1 ) locus has been associated with inflammatory disease and stroke in sickle cell anaemia. In the current work, we investigated the functional impact of VCAM-1 missense vari...
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| Veröffentlicht in: | Atherosclerosis 2013-10, Vol.230 (2), p.185-190 |
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| creator | Schmitz, Boris Vischer, Peter Brand, Eva Schmidt-Petersen, Klaus Korb-Pap, Adelheid Guske, Katrin Nedele, Johanna Schelleckes, Michael Hillen, Jan Rötrige, Alois Simmet, Thomas Paul, Martin Cambien, François Brand, Stefan-Martin |
| description | Abstract Objective In whole genome and single gene analyses, genetic variation at the vascular cell adhesion molecule-1 ( VCAM-1 ) locus has been associated with inflammatory disease and stroke in sickle cell anaemia. In the current work, we investigated the functional impact of VCAM-1 missense variants and their effect on cell–cell adhesion. Methods and results To determine the functional in vitro relevance of five missense VCAM-1 variants (S318F; T384A; G413A; L555V; I716L), we generated wild type and single variant VCAM-1 forms [318F, 384A, 413A, 555V, 716L] in EA.hy926 endothelial cells. Real-time PCR, western blot and ELISA analyses revealed significant differences in mRNA and protein levels for VCAM-1 variants. Monocytic cell lines THP-1 and U937 showed significantly increased adhesion to endothelial cells overexpressing VCAM-1 forms 318F, 555V and 716L compared to those overexpressing wild type VCAM-1 ( p |
| doi_str_mv | 10.1016/j.atherosclerosis.2013.07.039 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1438569883</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>1_s2_0_S0021915013004449</els_id><sourcerecordid>1438569883</sourcerecordid><originalsourceid>FETCH-LOGICAL-c453t-8b4e68b3de297210bb7c15332e1bb29c031825daac8010b8362361d6d4638c633</originalsourceid><addsrcrecordid>eNqNksFu1DAURa0K1A6FX4BskLpJ8LOdxFm0UjUqpVIRi1JWSJZjv6GeZuypnRkxf8O38GU4TOmiKzb24t1739XRI-Q90AooNB-WlR7vMIZkhul1qWIUeEXbivLugMxAtl0JQooXZEYpg7KDmh6RVyktKaWiBXlIjpigbd0KNiPfr7yJqBPaYhV8MLsRC23vMLngi35XoLch7xucHgr8uY6Y_k7Covg2P_9cQrFyKaFPWGx1dHqchs7__rV1YwyvycuFHhK-efyPye3Hi6_zT-X1l8ur-fl1aUTNx1L2AhvZc4usaxnQvm8N1JwzhL5nnaEcJKut1kbSPJW8YbwB21jRcGkazo_JyT53HcPDBtOociuDw6A9hk1SILism07KSXq6l5oML0VcqHV0Kx13CqiaAKulegZYTYAVbVUGnP1vH1dt-hXaJ_c_olnwbi9Y6KD0j5j9tzc5oZ7od4yLrLjcKzAj2TqMKhmH3qB1Ec2obHD_XebsWZIZnHdGD_e4w7QMm-gzdwUqMUXVzXQP0zkAz12E6PgfxSC1BQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1438569883</pqid></control><display><type>article</type><title>Increased monocyte adhesion by endothelial expression of VCAM-1 missense variation in vitro</title><source>MEDLINE</source><source>Access via ScienceDirect (Elsevier)</source><creator>Schmitz, Boris ; Vischer, Peter ; Brand, Eva ; Schmidt-Petersen, Klaus ; Korb-Pap, Adelheid ; Guske, Katrin ; Nedele, Johanna ; Schelleckes, Michael ; Hillen, Jan ; Rötrige, Alois ; Simmet, Thomas ; Paul, Martin ; Cambien, François ; Brand, Stefan-Martin</creator><creatorcontrib>Schmitz, Boris ; Vischer, Peter ; Brand, Eva ; Schmidt-Petersen, Klaus ; Korb-Pap, Adelheid ; Guske, Katrin ; Nedele, Johanna ; Schelleckes, Michael ; Hillen, Jan ; Rötrige, Alois ; Simmet, Thomas ; Paul, Martin ; Cambien, François ; Brand, Stefan-Martin</creatorcontrib><description>Abstract Objective In whole genome and single gene analyses, genetic variation at the vascular cell adhesion molecule-1 ( VCAM-1 ) locus has been associated with inflammatory disease and stroke in sickle cell anaemia. In the current work, we investigated the functional impact of VCAM-1 missense variants and their effect on cell–cell adhesion. Methods and results To determine the functional in vitro relevance of five missense VCAM-1 variants (S318F; T384A; G413A; L555V; I716L), we generated wild type and single variant VCAM-1 forms [318F, 384A, 413A, 555V, 716L] in EA.hy926 endothelial cells. Real-time PCR, western blot and ELISA analyses revealed significant differences in mRNA and protein levels for VCAM-1 variants. Monocytic cell lines THP-1 and U937 showed significantly increased adhesion to endothelial cells overexpressing VCAM-1 forms 318F, 555V and 716L compared to those overexpressing wild type VCAM-1 ( p < 0.05). Conclusions VCAM-1-dependent cell adhesion to endothelial cells in vitro is significantly increased when expressing VCAM-1 missense mutations 318F, 555V and 716L. The underlying mechanism involves altered VCAM-1 protein levels and function. This observation may be of particular relevance for chronic inflammatory pathophysiologic conditions involving cell–cell adhesion such as atherosclerosis and other proinflammatory conditions.</description><identifier>ISSN: 0021-9150</identifier><identifier>EISSN: 1879-1484</identifier><identifier>DOI: 10.1016/j.atherosclerosis.2013.07.039</identifier><identifier>PMID: 24075742</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>adhesion ; Alleles ; atherosclerosis ; Atherosclerosis - pathology ; Blotting, Western ; Cardiovascular ; Cardiovascular disease ; Cell Adhesion ; endothelial cells ; Endothelial Cells - cytology ; Endothelium, Vascular - pathology ; Enzyme-Linked Immunosorbent Assay ; Functional analyses ; genes ; genetic variation ; Humans ; Inflammation ; loci ; messenger RNA ; missense mutation ; Missense variants ; Monocyte adhesion ; Monocytes - cytology ; Mutation ; Mutation, Missense ; quantitative polymerase chain reaction ; Real-Time Polymerase Chain Reaction ; RNA, Messenger - metabolism ; sickle cell anemia ; stroke ; Time Factors ; U937 Cells ; Vascular Cell Adhesion Molecule-1 - genetics ; Vascular cell adhesion protein-1 ; Western blotting</subject><ispartof>Atherosclerosis, 2013-10, Vol.230 (2), p.185-190</ispartof><rights>Elsevier Ireland Ltd</rights><rights>2013 Elsevier Ireland Ltd</rights><rights>Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c453t-8b4e68b3de297210bb7c15332e1bb29c031825daac8010b8362361d6d4638c633</citedby><cites>FETCH-LOGICAL-c453t-8b4e68b3de297210bb7c15332e1bb29c031825daac8010b8362361d6d4638c633</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.atherosclerosis.2013.07.039$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24075742$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schmitz, Boris</creatorcontrib><creatorcontrib>Vischer, Peter</creatorcontrib><creatorcontrib>Brand, Eva</creatorcontrib><creatorcontrib>Schmidt-Petersen, Klaus</creatorcontrib><creatorcontrib>Korb-Pap, Adelheid</creatorcontrib><creatorcontrib>Guske, Katrin</creatorcontrib><creatorcontrib>Nedele, Johanna</creatorcontrib><creatorcontrib>Schelleckes, Michael</creatorcontrib><creatorcontrib>Hillen, Jan</creatorcontrib><creatorcontrib>Rötrige, Alois</creatorcontrib><creatorcontrib>Simmet, Thomas</creatorcontrib><creatorcontrib>Paul, Martin</creatorcontrib><creatorcontrib>Cambien, François</creatorcontrib><creatorcontrib>Brand, Stefan-Martin</creatorcontrib><title>Increased monocyte adhesion by endothelial expression of VCAM-1 missense variation in vitro</title><title>Atherosclerosis</title><addtitle>Atherosclerosis</addtitle><description>Abstract Objective In whole genome and single gene analyses, genetic variation at the vascular cell adhesion molecule-1 ( VCAM-1 ) locus has been associated with inflammatory disease and stroke in sickle cell anaemia. In the current work, we investigated the functional impact of VCAM-1 missense variants and their effect on cell–cell adhesion. Methods and results To determine the functional in vitro relevance of five missense VCAM-1 variants (S318F; T384A; G413A; L555V; I716L), we generated wild type and single variant VCAM-1 forms [318F, 384A, 413A, 555V, 716L] in EA.hy926 endothelial cells. Real-time PCR, western blot and ELISA analyses revealed significant differences in mRNA and protein levels for VCAM-1 variants. Monocytic cell lines THP-1 and U937 showed significantly increased adhesion to endothelial cells overexpressing VCAM-1 forms 318F, 555V and 716L compared to those overexpressing wild type VCAM-1 ( p < 0.05). Conclusions VCAM-1-dependent cell adhesion to endothelial cells in vitro is significantly increased when expressing VCAM-1 missense mutations 318F, 555V and 716L. The underlying mechanism involves altered VCAM-1 protein levels and function. This observation may be of particular relevance for chronic inflammatory pathophysiologic conditions involving cell–cell adhesion such as atherosclerosis and other proinflammatory conditions.</description><subject>adhesion</subject><subject>Alleles</subject><subject>atherosclerosis</subject><subject>Atherosclerosis - pathology</subject><subject>Blotting, Western</subject><subject>Cardiovascular</subject><subject>Cardiovascular disease</subject><subject>Cell Adhesion</subject><subject>endothelial cells</subject><subject>Endothelial Cells - cytology</subject><subject>Endothelium, Vascular - pathology</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Functional analyses</subject><subject>genes</subject><subject>genetic variation</subject><subject>Humans</subject><subject>Inflammation</subject><subject>loci</subject><subject>messenger RNA</subject><subject>missense mutation</subject><subject>Missense variants</subject><subject>Monocyte adhesion</subject><subject>Monocytes - cytology</subject><subject>Mutation</subject><subject>Mutation, Missense</subject><subject>quantitative polymerase chain reaction</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>RNA, Messenger - metabolism</subject><subject>sickle cell anemia</subject><subject>stroke</subject><subject>Time Factors</subject><subject>U937 Cells</subject><subject>Vascular Cell Adhesion Molecule-1 - genetics</subject><subject>Vascular cell adhesion protein-1</subject><subject>Western blotting</subject><issn>0021-9150</issn><issn>1879-1484</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNksFu1DAURa0K1A6FX4BskLpJ8LOdxFm0UjUqpVIRi1JWSJZjv6GeZuypnRkxf8O38GU4TOmiKzb24t1739XRI-Q90AooNB-WlR7vMIZkhul1qWIUeEXbivLugMxAtl0JQooXZEYpg7KDmh6RVyktKaWiBXlIjpigbd0KNiPfr7yJqBPaYhV8MLsRC23vMLngi35XoLch7xucHgr8uY6Y_k7Covg2P_9cQrFyKaFPWGx1dHqchs7__rV1YwyvycuFHhK-efyPye3Hi6_zT-X1l8ur-fl1aUTNx1L2AhvZc4usaxnQvm8N1JwzhL5nnaEcJKut1kbSPJW8YbwB21jRcGkazo_JyT53HcPDBtOociuDw6A9hk1SILism07KSXq6l5oML0VcqHV0Kx13CqiaAKulegZYTYAVbVUGnP1vH1dt-hXaJ_c_olnwbi9Y6KD0j5j9tzc5oZ7od4yLrLjcKzAj2TqMKhmH3qB1Ec2obHD_XebsWZIZnHdGD_e4w7QMm-gzdwUqMUXVzXQP0zkAz12E6PgfxSC1BQ</recordid><startdate>20131001</startdate><enddate>20131001</enddate><creator>Schmitz, Boris</creator><creator>Vischer, Peter</creator><creator>Brand, Eva</creator><creator>Schmidt-Petersen, Klaus</creator><creator>Korb-Pap, Adelheid</creator><creator>Guske, Katrin</creator><creator>Nedele, Johanna</creator><creator>Schelleckes, Michael</creator><creator>Hillen, Jan</creator><creator>Rötrige, Alois</creator><creator>Simmet, Thomas</creator><creator>Paul, Martin</creator><creator>Cambien, François</creator><creator>Brand, Stefan-Martin</creator><general>Elsevier Ireland Ltd</general><scope>6I.</scope><scope>AAFTH</scope><scope>FBQ</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>7X8</scope></search><sort><creationdate>20131001</creationdate><title>Increased monocyte adhesion by endothelial expression of VCAM-1 missense variation in vitro</title><author>Schmitz, Boris ; Vischer, Peter ; Brand, Eva ; Schmidt-Petersen, Klaus ; Korb-Pap, Adelheid ; Guske, Katrin ; Nedele, Johanna ; Schelleckes, Michael ; Hillen, Jan ; Rötrige, Alois ; Simmet, Thomas ; Paul, Martin ; Cambien, François ; Brand, Stefan-Martin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c453t-8b4e68b3de297210bb7c15332e1bb29c031825daac8010b8362361d6d4638c633</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>adhesion</topic><topic>Alleles</topic><topic>atherosclerosis</topic><topic>Atherosclerosis - pathology</topic><topic>Blotting, Western</topic><topic>Cardiovascular</topic><topic>Cardiovascular disease</topic><topic>Cell Adhesion</topic><topic>endothelial cells</topic><topic>Endothelial Cells - cytology</topic><topic>Endothelium, Vascular - pathology</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Functional analyses</topic><topic>genes</topic><topic>genetic variation</topic><topic>Humans</topic><topic>Inflammation</topic><topic>loci</topic><topic>messenger RNA</topic><topic>missense mutation</topic><topic>Missense variants</topic><topic>Monocyte adhesion</topic><topic>Monocytes - cytology</topic><topic>Mutation</topic><topic>Mutation, Missense</topic><topic>quantitative polymerase chain reaction</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>RNA, Messenger - metabolism</topic><topic>sickle cell anemia</topic><topic>stroke</topic><topic>Time Factors</topic><topic>U937 Cells</topic><topic>Vascular Cell Adhesion Molecule-1 - genetics</topic><topic>Vascular cell adhesion protein-1</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schmitz, Boris</creatorcontrib><creatorcontrib>Vischer, Peter</creatorcontrib><creatorcontrib>Brand, Eva</creatorcontrib><creatorcontrib>Schmidt-Petersen, Klaus</creatorcontrib><creatorcontrib>Korb-Pap, Adelheid</creatorcontrib><creatorcontrib>Guske, Katrin</creatorcontrib><creatorcontrib>Nedele, Johanna</creatorcontrib><creatorcontrib>Schelleckes, Michael</creatorcontrib><creatorcontrib>Hillen, Jan</creatorcontrib><creatorcontrib>Rötrige, Alois</creatorcontrib><creatorcontrib>Simmet, Thomas</creatorcontrib><creatorcontrib>Paul, Martin</creatorcontrib><creatorcontrib>Cambien, François</creatorcontrib><creatorcontrib>Brand, Stefan-Martin</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>AGRIS</collection><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>Atherosclerosis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schmitz, Boris</au><au>Vischer, Peter</au><au>Brand, Eva</au><au>Schmidt-Petersen, Klaus</au><au>Korb-Pap, Adelheid</au><au>Guske, Katrin</au><au>Nedele, Johanna</au><au>Schelleckes, Michael</au><au>Hillen, Jan</au><au>Rötrige, Alois</au><au>Simmet, Thomas</au><au>Paul, Martin</au><au>Cambien, François</au><au>Brand, Stefan-Martin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased monocyte adhesion by endothelial expression of VCAM-1 missense variation in vitro</atitle><jtitle>Atherosclerosis</jtitle><addtitle>Atherosclerosis</addtitle><date>2013-10-01</date><risdate>2013</risdate><volume>230</volume><issue>2</issue><spage>185</spage><epage>190</epage><pages>185-190</pages><issn>0021-9150</issn><eissn>1879-1484</eissn><abstract>Abstract Objective In whole genome and single gene analyses, genetic variation at the vascular cell adhesion molecule-1 ( VCAM-1 ) locus has been associated with inflammatory disease and stroke in sickle cell anaemia. In the current work, we investigated the functional impact of VCAM-1 missense variants and their effect on cell–cell adhesion. Methods and results To determine the functional in vitro relevance of five missense VCAM-1 variants (S318F; T384A; G413A; L555V; I716L), we generated wild type and single variant VCAM-1 forms [318F, 384A, 413A, 555V, 716L] in EA.hy926 endothelial cells. Real-time PCR, western blot and ELISA analyses revealed significant differences in mRNA and protein levels for VCAM-1 variants. Monocytic cell lines THP-1 and U937 showed significantly increased adhesion to endothelial cells overexpressing VCAM-1 forms 318F, 555V and 716L compared to those overexpressing wild type VCAM-1 ( p < 0.05). Conclusions VCAM-1-dependent cell adhesion to endothelial cells in vitro is significantly increased when expressing VCAM-1 missense mutations 318F, 555V and 716L. The underlying mechanism involves altered VCAM-1 protein levels and function. This observation may be of particular relevance for chronic inflammatory pathophysiologic conditions involving cell–cell adhesion such as atherosclerosis and other proinflammatory conditions.</abstract><cop>Ireland</cop><pub>Elsevier Ireland Ltd</pub><pmid>24075742</pmid><doi>10.1016/j.atherosclerosis.2013.07.039</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | adhesion Alleles atherosclerosis Atherosclerosis - pathology Blotting, Western Cardiovascular Cardiovascular disease Cell Adhesion endothelial cells Endothelial Cells - cytology Endothelium, Vascular - pathology Enzyme-Linked Immunosorbent Assay Functional analyses genes genetic variation Humans Inflammation loci messenger RNA missense mutation Missense variants Monocyte adhesion Monocytes - cytology Mutation Mutation, Missense quantitative polymerase chain reaction Real-Time Polymerase Chain Reaction RNA, Messenger - metabolism sickle cell anemia stroke Time Factors U937 Cells Vascular Cell Adhesion Molecule-1 - genetics Vascular cell adhesion protein-1 Western blotting |
| title | Increased monocyte adhesion by endothelial expression of VCAM-1 missense variation in vitro |
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