Expression and Cellular Localization of CXCR4 and CXCL12 in Human Carotid Atherosclerotic Plaques
Abstract Background and Aims The CXCR4/CXCL12 complex has already been associated with progression of atherosclerosis; however, its exact role is yet unknown. The aim of this study was to analyse the expression and cellular localization of CXCL12 and its receptor CXCR4 in human carotid atherosclero...
Gespeichert in:
| Veröffentlicht in: | Thrombosis and haemostasis 2018, Vol.118 (1), p.195-206 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 206 |
|---|---|
| container_issue | 1 |
| container_start_page | 195 |
| container_title | Thrombosis and haemostasis |
| container_volume | 118 |
| creator | Merckelbach, Sophie van der Vorst, Emiel P. C. Kallmayer, Michael Rischpler, Christoph Burgkart, Rainer Döring, Yvonne de Borst, Gert-Jan Schwaiger, Markus Eckstein, Hans-Henning Weber, Christian Pelisek, Jaroslav |
| description | Abstract
Background and Aims
The CXCR4/CXCL12 complex has already been associated with progression of atherosclerosis; however, its exact role is yet unknown. The aim of this study was to analyse the expression and cellular localization of CXCL12 and its receptor CXCR4 in human carotid atherosclerotic plaques.
Methods
Carotid plaques (
n
= 58; 31 stable, 27 unstable, based on histological characterization of plaque morphology) were obtained during carotid endarterectomy, and 10 healthy vessels were used as a control. Expression of
cxcr4
,
cxcr7
,
cxcl12
,
ccl2/ccr2
and
csf1/csf1r
was analysed at mRNA, and level expression of CXCR4, CXCR7 and CXCL12 was analysed at protein level. Cellular localization was determined using consecutive and double immunohistochemical (IHC) staining and microdissection.
Results
At mRNA level,
cxcr4, cxcr7
and
cxcl12
were significantly higher expressed in stable carotid plaques compared with controls (
p
= 0.011,
p
|
| doi_str_mv | 10.1160/TH17-04-0271 |
| format | Article |
| fullrecord | <record><control><sourceid>pubmed_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1160_TH17_04_0271</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>29304539</sourcerecordid><originalsourceid>FETCH-LOGICAL-c436t-8af4527cdaed6ff10183c54684dd2e490ad71309bc2201baee2d38c67cf2459b3</originalsourceid><addsrcrecordid>eNptkE1Lw0AQhhdRbK3ePMveNTr7kU1yLEu1QkCRCr2Fze6GpuSj7iZg_fUmRD15GoZ5eJn3QeiawD0hAh42axIFwAOgETlBcxqKKBBxsj1Fc2AcAkF5OEMX3u8BiOBJeI5mNGHAQ5bMkVp9Hpz1vmwbrBqDpa2qvlIOp61WVfmluvHSFlhu5RufkK1MCcVlg9d9rRoslWu70uBlt7Ou9bqy467xa6U-eusv0VmhKm-vfuYCvT-uNnIdpC9Pz3KZBpoz0QWxKnhII22UNaIoCJCY6ZCLmBtDLU9AmYgwSHJNKZBcWUsNi7WIdDEUTHK2QHdTrh6e8M4W2cGVtXLHjEA2mspGUxnwbDQ14DcTfujz2po_-FfNANxOQLcrbW2zfdu7Zijwf9w31oRw3A</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Expression and Cellular Localization of CXCR4 and CXCL12 in Human Carotid Atherosclerotic Plaques</title><source>MEDLINE</source><source>Thieme Connect Journals</source><creator>Merckelbach, Sophie ; van der Vorst, Emiel P. C. ; Kallmayer, Michael ; Rischpler, Christoph ; Burgkart, Rainer ; Döring, Yvonne ; de Borst, Gert-Jan ; Schwaiger, Markus ; Eckstein, Hans-Henning ; Weber, Christian ; Pelisek, Jaroslav</creator><creatorcontrib>Merckelbach, Sophie ; van der Vorst, Emiel P. C. ; Kallmayer, Michael ; Rischpler, Christoph ; Burgkart, Rainer ; Döring, Yvonne ; de Borst, Gert-Jan ; Schwaiger, Markus ; Eckstein, Hans-Henning ; Weber, Christian ; Pelisek, Jaroslav</creatorcontrib><description>Abstract
Background and Aims
The CXCR4/CXCL12 complex has already been associated with progression of atherosclerosis; however, its exact role is yet unknown. The aim of this study was to analyse the expression and cellular localization of CXCL12 and its receptor CXCR4 in human carotid atherosclerotic plaques.
Methods
Carotid plaques (
n
= 58; 31 stable, 27 unstable, based on histological characterization of plaque morphology) were obtained during carotid endarterectomy, and 10 healthy vessels were used as a control. Expression of
cxcr4
,
cxcr7
,
cxcl12
,
ccl2/ccr2
and
csf1/csf1r
was analysed at mRNA, and level expression of CXCR4, CXCR7 and CXCL12 was analysed at protein level. Cellular localization was determined using consecutive and double immunohistochemical (IHC) staining and microdissection.
Results
At mRNA level,
cxcr4, cxcr7
and
cxcl12
were significantly higher expressed in stable carotid plaques compared with controls (
p
= 0.011,
p
< 0.001 and
p
< 0.001).
Cxcl12
mRNA expression was successively augmented toward unstable plaques (
p
< 0.001). At protein level, CXCR4, CXCR7 and CXCL12 expression was significantly increased in both stable (
p
= 0.001,
p
< 0.001 and
p
= 0.035, respectively) and unstable (
p
= 0.003,
p
< 0.001 and
p
= 0.045, respectively) plaques compared with controls. Using IHC, CXCR4 was particularly localized in macrophages and small neovessels. Microdissection confirmed strongest expression of
cxcr4
in macrophages within atherosclerotic plaques. Leukocytes and smooth muscle cells showed
cxcr4
expression as well. For
cxcl12
, only microdissected areas with macrophages were positive.
Conclusion
Expression of CXCR4 and CXCL12 was significantly increased in both stable and unstable carotid atherosclerotic plaques compared with healthy vessels, both at mRNA and protein level. CXCR4 and CXCL12 were localized particularly in macrophages.</description><identifier>ISSN: 0340-6245</identifier><identifier>EISSN: 2567-689X</identifier><identifier>DOI: 10.1160/TH17-04-0271</identifier><identifier>PMID: 29304539</identifier><language>eng</language><publisher>Stuttgart: Schattauer GmbH</publisher><subject>Aged ; Atherosclerosis ; Atherosclerosis and Ischaemic Disease ; Carotid Arteries - metabolism ; Chemokine CCL2 - metabolism ; Chemokine CXCL12 - metabolism ; Disease Progression ; Endarterectomy, Carotid ; Female ; Gene Expression Profiling ; Gene Expression Regulation ; Humans ; Immunohistochemistry ; Macrophage Colony-Stimulating Factor - metabolism ; Male ; Middle Aged ; Plaque, Atherosclerotic - metabolism ; Receptors, CCR2 - metabolism ; Receptors, CXCR - metabolism ; Receptors, CXCR4 - metabolism ; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor - metabolism ; RNA, Messenger - metabolism</subject><ispartof>Thrombosis and haemostasis, 2018, Vol.118 (1), p.195-206</ispartof><rights>Schattauer GmbH Stuttgart.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c436t-8af4527cdaed6ff10183c54684dd2e490ad71309bc2201baee2d38c67cf2459b3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.thieme-connect.de/products/ejournals/pdf/10.1160/TH17-04-0271.pdf$$EPDF$$P50$$Gthieme$$H</linktopdf><linktohtml>$$Uhttps://www.thieme-connect.de/products/ejournals/html/10.1160/TH17-04-0271$$EHTML$$P50$$Gthieme$$H</linktohtml><link.rule.ids>314,776,780,3005,4010,27900,27901,27902,54534,54535</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29304539$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Merckelbach, Sophie</creatorcontrib><creatorcontrib>van der Vorst, Emiel P. C.</creatorcontrib><creatorcontrib>Kallmayer, Michael</creatorcontrib><creatorcontrib>Rischpler, Christoph</creatorcontrib><creatorcontrib>Burgkart, Rainer</creatorcontrib><creatorcontrib>Döring, Yvonne</creatorcontrib><creatorcontrib>de Borst, Gert-Jan</creatorcontrib><creatorcontrib>Schwaiger, Markus</creatorcontrib><creatorcontrib>Eckstein, Hans-Henning</creatorcontrib><creatorcontrib>Weber, Christian</creatorcontrib><creatorcontrib>Pelisek, Jaroslav</creatorcontrib><title>Expression and Cellular Localization of CXCR4 and CXCL12 in Human Carotid Atherosclerotic Plaques</title><title>Thrombosis and haemostasis</title><addtitle>Thromb Haemost</addtitle><description>Abstract
Background and Aims
The CXCR4/CXCL12 complex has already been associated with progression of atherosclerosis; however, its exact role is yet unknown. The aim of this study was to analyse the expression and cellular localization of CXCL12 and its receptor CXCR4 in human carotid atherosclerotic plaques.
Methods
Carotid plaques (
n
= 58; 31 stable, 27 unstable, based on histological characterization of plaque morphology) were obtained during carotid endarterectomy, and 10 healthy vessels were used as a control. Expression of
cxcr4
,
cxcr7
,
cxcl12
,
ccl2/ccr2
and
csf1/csf1r
was analysed at mRNA, and level expression of CXCR4, CXCR7 and CXCL12 was analysed at protein level. Cellular localization was determined using consecutive and double immunohistochemical (IHC) staining and microdissection.
Results
At mRNA level,
cxcr4, cxcr7
and
cxcl12
were significantly higher expressed in stable carotid plaques compared with controls (
p
= 0.011,
p
< 0.001 and
p
< 0.001).
Cxcl12
mRNA expression was successively augmented toward unstable plaques (
p
< 0.001). At protein level, CXCR4, CXCR7 and CXCL12 expression was significantly increased in both stable (
p
= 0.001,
p
< 0.001 and
p
= 0.035, respectively) and unstable (
p
= 0.003,
p
< 0.001 and
p
= 0.045, respectively) plaques compared with controls. Using IHC, CXCR4 was particularly localized in macrophages and small neovessels. Microdissection confirmed strongest expression of
cxcr4
in macrophages within atherosclerotic plaques. Leukocytes and smooth muscle cells showed
cxcr4
expression as well. For
cxcl12
, only microdissected areas with macrophages were positive.
Conclusion
Expression of CXCR4 and CXCL12 was significantly increased in both stable and unstable carotid atherosclerotic plaques compared with healthy vessels, both at mRNA and protein level. CXCR4 and CXCL12 were localized particularly in macrophages.</description><subject>Aged</subject><subject>Atherosclerosis</subject><subject>Atherosclerosis and Ischaemic Disease</subject><subject>Carotid Arteries - metabolism</subject><subject>Chemokine CCL2 - metabolism</subject><subject>Chemokine CXCL12 - metabolism</subject><subject>Disease Progression</subject><subject>Endarterectomy, Carotid</subject><subject>Female</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Macrophage Colony-Stimulating Factor - metabolism</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Plaque, Atherosclerotic - metabolism</subject><subject>Receptors, CCR2 - metabolism</subject><subject>Receptors, CXCR - metabolism</subject><subject>Receptors, CXCR4 - metabolism</subject><subject>Receptors, Granulocyte-Macrophage Colony-Stimulating Factor - metabolism</subject><subject>RNA, Messenger - metabolism</subject><issn>0340-6245</issn><issn>2567-689X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkE1Lw0AQhhdRbK3ePMveNTr7kU1yLEu1QkCRCr2Fze6GpuSj7iZg_fUmRD15GoZ5eJn3QeiawD0hAh42axIFwAOgETlBcxqKKBBxsj1Fc2AcAkF5OEMX3u8BiOBJeI5mNGHAQ5bMkVp9Hpz1vmwbrBqDpa2qvlIOp61WVfmluvHSFlhu5RufkK1MCcVlg9d9rRoslWu70uBlt7Ou9bqy467xa6U-eusv0VmhKm-vfuYCvT-uNnIdpC9Pz3KZBpoz0QWxKnhII22UNaIoCJCY6ZCLmBtDLU9AmYgwSHJNKZBcWUsNi7WIdDEUTHK2QHdTrh6e8M4W2cGVtXLHjEA2mspGUxnwbDQ14DcTfujz2po_-FfNANxOQLcrbW2zfdu7Zijwf9w31oRw3A</recordid><startdate>2018</startdate><enddate>2018</enddate><creator>Merckelbach, Sophie</creator><creator>van der Vorst, Emiel P. C.</creator><creator>Kallmayer, Michael</creator><creator>Rischpler, Christoph</creator><creator>Burgkart, Rainer</creator><creator>Döring, Yvonne</creator><creator>de Borst, Gert-Jan</creator><creator>Schwaiger, Markus</creator><creator>Eckstein, Hans-Henning</creator><creator>Weber, Christian</creator><creator>Pelisek, Jaroslav</creator><general>Schattauer GmbH</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></search><sort><creationdate>2018</creationdate><title>Expression and Cellular Localization of CXCR4 and CXCL12 in Human Carotid Atherosclerotic Plaques</title><author>Merckelbach, Sophie ; van der Vorst, Emiel P. C. ; Kallmayer, Michael ; Rischpler, Christoph ; Burgkart, Rainer ; Döring, Yvonne ; de Borst, Gert-Jan ; Schwaiger, Markus ; Eckstein, Hans-Henning ; Weber, Christian ; Pelisek, Jaroslav</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c436t-8af4527cdaed6ff10183c54684dd2e490ad71309bc2201baee2d38c67cf2459b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Aged</topic><topic>Atherosclerosis</topic><topic>Atherosclerosis and Ischaemic Disease</topic><topic>Carotid Arteries - metabolism</topic><topic>Chemokine CCL2 - metabolism</topic><topic>Chemokine CXCL12 - metabolism</topic><topic>Disease Progression</topic><topic>Endarterectomy, Carotid</topic><topic>Female</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Macrophage Colony-Stimulating Factor - metabolism</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Plaque, Atherosclerotic - metabolism</topic><topic>Receptors, CCR2 - metabolism</topic><topic>Receptors, CXCR - metabolism</topic><topic>Receptors, CXCR4 - metabolism</topic><topic>Receptors, Granulocyte-Macrophage Colony-Stimulating Factor - metabolism</topic><topic>RNA, Messenger - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Merckelbach, Sophie</creatorcontrib><creatorcontrib>van der Vorst, Emiel P. C.</creatorcontrib><creatorcontrib>Kallmayer, Michael</creatorcontrib><creatorcontrib>Rischpler, Christoph</creatorcontrib><creatorcontrib>Burgkart, Rainer</creatorcontrib><creatorcontrib>Döring, Yvonne</creatorcontrib><creatorcontrib>de Borst, Gert-Jan</creatorcontrib><creatorcontrib>Schwaiger, Markus</creatorcontrib><creatorcontrib>Eckstein, Hans-Henning</creatorcontrib><creatorcontrib>Weber, Christian</creatorcontrib><creatorcontrib>Pelisek, Jaroslav</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Thrombosis and haemostasis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Merckelbach, Sophie</au><au>van der Vorst, Emiel P. C.</au><au>Kallmayer, Michael</au><au>Rischpler, Christoph</au><au>Burgkart, Rainer</au><au>Döring, Yvonne</au><au>de Borst, Gert-Jan</au><au>Schwaiger, Markus</au><au>Eckstein, Hans-Henning</au><au>Weber, Christian</au><au>Pelisek, Jaroslav</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression and Cellular Localization of CXCR4 and CXCL12 in Human Carotid Atherosclerotic Plaques</atitle><jtitle>Thrombosis and haemostasis</jtitle><addtitle>Thromb Haemost</addtitle><date>2018</date><risdate>2018</risdate><volume>118</volume><issue>1</issue><spage>195</spage><epage>206</epage><pages>195-206</pages><issn>0340-6245</issn><eissn>2567-689X</eissn><abstract>Abstract
Background and Aims
The CXCR4/CXCL12 complex has already been associated with progression of atherosclerosis; however, its exact role is yet unknown. The aim of this study was to analyse the expression and cellular localization of CXCL12 and its receptor CXCR4 in human carotid atherosclerotic plaques.
Methods
Carotid plaques (
n
= 58; 31 stable, 27 unstable, based on histological characterization of plaque morphology) were obtained during carotid endarterectomy, and 10 healthy vessels were used as a control. Expression of
cxcr4
,
cxcr7
,
cxcl12
,
ccl2/ccr2
and
csf1/csf1r
was analysed at mRNA, and level expression of CXCR4, CXCR7 and CXCL12 was analysed at protein level. Cellular localization was determined using consecutive and double immunohistochemical (IHC) staining and microdissection.
Results
At mRNA level,
cxcr4, cxcr7
and
cxcl12
were significantly higher expressed in stable carotid plaques compared with controls (
p
= 0.011,
p
< 0.001 and
p
< 0.001).
Cxcl12
mRNA expression was successively augmented toward unstable plaques (
p
< 0.001). At protein level, CXCR4, CXCR7 and CXCL12 expression was significantly increased in both stable (
p
= 0.001,
p
< 0.001 and
p
= 0.035, respectively) and unstable (
p
= 0.003,
p
< 0.001 and
p
= 0.045, respectively) plaques compared with controls. Using IHC, CXCR4 was particularly localized in macrophages and small neovessels. Microdissection confirmed strongest expression of
cxcr4
in macrophages within atherosclerotic plaques. Leukocytes and smooth muscle cells showed
cxcr4
expression as well. For
cxcl12
, only microdissected areas with macrophages were positive.
Conclusion
Expression of CXCR4 and CXCL12 was significantly increased in both stable and unstable carotid atherosclerotic plaques compared with healthy vessels, both at mRNA and protein level. CXCR4 and CXCL12 were localized particularly in macrophages.</abstract><cop>Stuttgart</cop><pub>Schattauer GmbH</pub><pmid>29304539</pmid><doi>10.1160/TH17-04-0271</doi><tpages>12</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0340-6245 |
| ispartof | Thrombosis and haemostasis, 2018, Vol.118 (1), p.195-206 |
| issn | 0340-6245 2567-689X |
| language | eng |
| recordid | cdi_crossref_primary_10_1160_TH17_04_0271 |
| source | MEDLINE; Thieme Connect Journals |
| subjects | Aged Atherosclerosis Atherosclerosis and Ischaemic Disease Carotid Arteries - metabolism Chemokine CCL2 - metabolism Chemokine CXCL12 - metabolism Disease Progression Endarterectomy, Carotid Female Gene Expression Profiling Gene Expression Regulation Humans Immunohistochemistry Macrophage Colony-Stimulating Factor - metabolism Male Middle Aged Plaque, Atherosclerotic - metabolism Receptors, CCR2 - metabolism Receptors, CXCR - metabolism Receptors, CXCR4 - metabolism Receptors, Granulocyte-Macrophage Colony-Stimulating Factor - metabolism RNA, Messenger - metabolism |
| title | Expression and Cellular Localization of CXCR4 and CXCL12 in Human Carotid Atherosclerotic Plaques |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-03T13%3A47%3A22IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmed_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Expression%20and%20Cellular%20Localization%20of%20CXCR4%20and%20CXCL12%20in%20Human%20Carotid%20Atherosclerotic%20Plaques&rft.jtitle=Thrombosis%20and%20haemostasis&rft.au=Merckelbach,%20Sophie&rft.date=2018&rft.volume=118&rft.issue=1&rft.spage=195&rft.epage=206&rft.pages=195-206&rft.issn=0340-6245&rft.eissn=2567-689X&rft_id=info:doi/10.1160/TH17-04-0271&rft_dat=%3Cpubmed_cross%3E29304539%3C/pubmed_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/29304539&rfr_iscdi=true |