LXR as a novel antithrombotic target
Liver X receptors (LXRs) are transcription factors involved in the regulation of cholesterol homeostasis. LXR ligands have athero-protective properties independent of their effects on cholesterol metabolism. Platelets are involved in the initiation of atherosclerosis and despite being anucleate expr...
Gespeichert in:
| Veröffentlicht in: | Blood 2011-05, Vol.117 (21), p.5751-5761 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 5761 |
|---|---|
| container_issue | 21 |
| container_start_page | 5751 |
| container_title | Blood |
| container_volume | 117 |
| creator | Spyridon, Michael Moraes, Leonardo A. Jones, Chris I. Sage, Tanya Sasikumar, Parvathy Bucci, Giovanna Gibbins, Jonathan M. |
| description | Liver X receptors (LXRs) are transcription factors involved in the regulation of cholesterol homeostasis. LXR ligands have athero-protective properties independent of their effects on cholesterol metabolism. Platelets are involved in the initiation of atherosclerosis and despite being anucleate express nuclear receptors. We hypothesized that the athero-protective effects of LXR ligands could be in part mediated through platelets and therefore explored the potential role of LXR in platelets. Our results show that LXR-β is present in human platelets and the LXR ligands, GW3965 and T0901317, modulated nongenomically platelet aggregation stimulated by a range of agonists. GW3965 caused LXR to associate with signaling components proximal to the collagen receptor, GPVI, suggesting a potential mechanism of LXR action in platelets that leads to diminished platelet responses. Activation of platelets at sites of atherosclerotic lesions results in thrombosis preceding myocardial infarction and stroke. Using an in vivo model of thrombosis in mice, we show that GW3965 has antithrombotic effects, reducing the size and the stability of thrombi. The athero-protective effects of GW3965, together with its novel antiplatelet/thrombotic effects, indicate LXR as a potential target for prevention of athero-thrombotic disease. |
| doi_str_mv | 10.1182/blood-2010-09-306142 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3110032</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0006497120450517</els_id><sourcerecordid>869000187</sourcerecordid><originalsourceid>FETCH-LOGICAL-c492t-f3a28e0aed214e7a6bebe6f4e0f7f91e343a4bed0361867aaeb8f2409d6144f53</originalsourceid><addsrcrecordid>eNp9kE1r3DAQhkVpaTZp_0EoPjTk5GZG0sr2JRBCv2ChUFLoTYzlUaLgtRJJu5B_X6e7TdpLT3PQM--8eoQ4RviA2MqzfoxxqCUg1NDVCgxq-UIscCnbGkDCS7EAAFPrrsEDcZjzLQBqJZevxYFEjdgYWIj3q5_fK8oVVVPc8ljRVEK5SXHdxxJcVShdc3kjXnkaM7_dzyPx49PHq8sv9erb56-XF6va6U6W2iuSLQPxMOdzQ6bnno3XDL7xHbLSinTPAyiDrWmIuG-91NANc3ftl-pInO9y7zb9mgfHU0k02rsU1pQebKRg_32Zwo29jlurEAGUnANO9wEp3m84F7sO2fE40sRxk21rutkJts1M6h3pUsw5sX-6gmAf_drffu2jXwud3fmd19793fBp6Y_QGTjZA5QdjT7R5EJ-5rQE1S7N81d59rkNnGx2gSfHQ0jsih1i-H-TXznLmQ8</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>869000187</pqid></control><display><type>article</type><title>LXR as a novel antithrombotic target</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Spyridon, Michael ; Moraes, Leonardo A. ; Jones, Chris I. ; Sage, Tanya ; Sasikumar, Parvathy ; Bucci, Giovanna ; Gibbins, Jonathan M.</creator><creatorcontrib>Spyridon, Michael ; Moraes, Leonardo A. ; Jones, Chris I. ; Sage, Tanya ; Sasikumar, Parvathy ; Bucci, Giovanna ; Gibbins, Jonathan M.</creatorcontrib><description>Liver X receptors (LXRs) are transcription factors involved in the regulation of cholesterol homeostasis. LXR ligands have athero-protective properties independent of their effects on cholesterol metabolism. Platelets are involved in the initiation of atherosclerosis and despite being anucleate express nuclear receptors. We hypothesized that the athero-protective effects of LXR ligands could be in part mediated through platelets and therefore explored the potential role of LXR in platelets. Our results show that LXR-β is present in human platelets and the LXR ligands, GW3965 and T0901317, modulated nongenomically platelet aggregation stimulated by a range of agonists. GW3965 caused LXR to associate with signaling components proximal to the collagen receptor, GPVI, suggesting a potential mechanism of LXR action in platelets that leads to diminished platelet responses. Activation of platelets at sites of atherosclerotic lesions results in thrombosis preceding myocardial infarction and stroke. Using an in vivo model of thrombosis in mice, we show that GW3965 has antithrombotic effects, reducing the size and the stability of thrombi. The athero-protective effects of GW3965, together with its novel antiplatelet/thrombotic effects, indicate LXR as a potential target for prevention of athero-thrombotic disease.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2010-09-306142</identifier><identifier>PMID: 21411760</identifier><language>eng</language><publisher>Washington, DC: Elsevier Inc</publisher><subject>Animals ; Atherosclerosis - complications ; Benzoates - therapeutic use ; Benzylamines - therapeutic use ; Biological and medical sciences ; Calcium - metabolism ; Flow Cytometry ; Hematologic and hematopoietic diseases ; Humans ; Hydrocarbons, Fluorinated - therapeutic use ; Immunoblotting ; Immunoprecipitation ; Ligands ; Liver X Receptors ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Orphan Nuclear Receptors - metabolism ; Platelet Aggregation - drug effects ; Platelet Glycoprotein GPIIb-IIIa Complex - metabolism ; Platelet Membrane Glycoproteins - metabolism ; Sulfonamides - therapeutic use ; Thrombosis - etiology ; Thrombosis - prevention & control ; Thrombosis and Hemostasis</subject><ispartof>Blood, 2011-05, Vol.117 (21), p.5751-5761</ispartof><rights>2011 American Society of Hematology</rights><rights>2015 INIST-CNRS</rights><rights>2011 by The American Society of Hematology 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c492t-f3a28e0aed214e7a6bebe6f4e0f7f91e343a4bed0361867aaeb8f2409d6144f53</citedby><cites>FETCH-LOGICAL-c492t-f3a28e0aed214e7a6bebe6f4e0f7f91e343a4bed0361867aaeb8f2409d6144f53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24203856$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21411760$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Spyridon, Michael</creatorcontrib><creatorcontrib>Moraes, Leonardo A.</creatorcontrib><creatorcontrib>Jones, Chris I.</creatorcontrib><creatorcontrib>Sage, Tanya</creatorcontrib><creatorcontrib>Sasikumar, Parvathy</creatorcontrib><creatorcontrib>Bucci, Giovanna</creatorcontrib><creatorcontrib>Gibbins, Jonathan M.</creatorcontrib><title>LXR as a novel antithrombotic target</title><title>Blood</title><addtitle>Blood</addtitle><description>Liver X receptors (LXRs) are transcription factors involved in the regulation of cholesterol homeostasis. LXR ligands have athero-protective properties independent of their effects on cholesterol metabolism. Platelets are involved in the initiation of atherosclerosis and despite being anucleate express nuclear receptors. We hypothesized that the athero-protective effects of LXR ligands could be in part mediated through platelets and therefore explored the potential role of LXR in platelets. Our results show that LXR-β is present in human platelets and the LXR ligands, GW3965 and T0901317, modulated nongenomically platelet aggregation stimulated by a range of agonists. GW3965 caused LXR to associate with signaling components proximal to the collagen receptor, GPVI, suggesting a potential mechanism of LXR action in platelets that leads to diminished platelet responses. Activation of platelets at sites of atherosclerotic lesions results in thrombosis preceding myocardial infarction and stroke. Using an in vivo model of thrombosis in mice, we show that GW3965 has antithrombotic effects, reducing the size and the stability of thrombi. The athero-protective effects of GW3965, together with its novel antiplatelet/thrombotic effects, indicate LXR as a potential target for prevention of athero-thrombotic disease.</description><subject>Animals</subject><subject>Atherosclerosis - complications</subject><subject>Benzoates - therapeutic use</subject><subject>Benzylamines - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Calcium - metabolism</subject><subject>Flow Cytometry</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Humans</subject><subject>Hydrocarbons, Fluorinated - therapeutic use</subject><subject>Immunoblotting</subject><subject>Immunoprecipitation</subject><subject>Ligands</subject><subject>Liver X Receptors</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Orphan Nuclear Receptors - metabolism</subject><subject>Platelet Aggregation - drug effects</subject><subject>Platelet Glycoprotein GPIIb-IIIa Complex - metabolism</subject><subject>Platelet Membrane Glycoproteins - metabolism</subject><subject>Sulfonamides - therapeutic use</subject><subject>Thrombosis - etiology</subject><subject>Thrombosis - prevention & control</subject><subject>Thrombosis and Hemostasis</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1r3DAQhkVpaTZp_0EoPjTk5GZG0sr2JRBCv2ChUFLoTYzlUaLgtRJJu5B_X6e7TdpLT3PQM--8eoQ4RviA2MqzfoxxqCUg1NDVCgxq-UIscCnbGkDCS7EAAFPrrsEDcZjzLQBqJZevxYFEjdgYWIj3q5_fK8oVVVPc8ljRVEK5SXHdxxJcVShdc3kjXnkaM7_dzyPx49PHq8sv9erb56-XF6va6U6W2iuSLQPxMOdzQ6bnno3XDL7xHbLSinTPAyiDrWmIuG-91NANc3ftl-pInO9y7zb9mgfHU0k02rsU1pQebKRg_32Zwo29jlurEAGUnANO9wEp3m84F7sO2fE40sRxk21rutkJts1M6h3pUsw5sX-6gmAf_drffu2jXwud3fmd19793fBp6Y_QGTjZA5QdjT7R5EJ-5rQE1S7N81d59rkNnGx2gSfHQ0jsih1i-H-TXznLmQ8</recordid><startdate>20110526</startdate><enddate>20110526</enddate><creator>Spyridon, Michael</creator><creator>Moraes, Leonardo A.</creator><creator>Jones, Chris I.</creator><creator>Sage, Tanya</creator><creator>Sasikumar, Parvathy</creator><creator>Bucci, Giovanna</creator><creator>Gibbins, Jonathan M.</creator><general>Elsevier Inc</general><general>Americain Society of Hematology</general><general>American Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</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><scope>5PM</scope></search><sort><creationdate>20110526</creationdate><title>LXR as a novel antithrombotic target</title><author>Spyridon, Michael ; Moraes, Leonardo A. ; Jones, Chris I. ; Sage, Tanya ; Sasikumar, Parvathy ; Bucci, Giovanna ; Gibbins, Jonathan M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c492t-f3a28e0aed214e7a6bebe6f4e0f7f91e343a4bed0361867aaeb8f2409d6144f53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Atherosclerosis - complications</topic><topic>Benzoates - therapeutic use</topic><topic>Benzylamines - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Calcium - metabolism</topic><topic>Flow Cytometry</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Humans</topic><topic>Hydrocarbons, Fluorinated - therapeutic use</topic><topic>Immunoblotting</topic><topic>Immunoprecipitation</topic><topic>Ligands</topic><topic>Liver X Receptors</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Orphan Nuclear Receptors - metabolism</topic><topic>Platelet Aggregation - drug effects</topic><topic>Platelet Glycoprotein GPIIb-IIIa Complex - metabolism</topic><topic>Platelet Membrane Glycoproteins - metabolism</topic><topic>Sulfonamides - therapeutic use</topic><topic>Thrombosis - etiology</topic><topic>Thrombosis - prevention & control</topic><topic>Thrombosis and Hemostasis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Spyridon, Michael</creatorcontrib><creatorcontrib>Moraes, Leonardo A.</creatorcontrib><creatorcontrib>Jones, Chris I.</creatorcontrib><creatorcontrib>Sage, Tanya</creatorcontrib><creatorcontrib>Sasikumar, Parvathy</creatorcontrib><creatorcontrib>Bucci, Giovanna</creatorcontrib><creatorcontrib>Gibbins, Jonathan M.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Spyridon, Michael</au><au>Moraes, Leonardo A.</au><au>Jones, Chris I.</au><au>Sage, Tanya</au><au>Sasikumar, Parvathy</au><au>Bucci, Giovanna</au><au>Gibbins, Jonathan M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>LXR as a novel antithrombotic target</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>2011-05-26</date><risdate>2011</risdate><volume>117</volume><issue>21</issue><spage>5751</spage><epage>5761</epage><pages>5751-5761</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>Liver X receptors (LXRs) are transcription factors involved in the regulation of cholesterol homeostasis. LXR ligands have athero-protective properties independent of their effects on cholesterol metabolism. Platelets are involved in the initiation of atherosclerosis and despite being anucleate express nuclear receptors. We hypothesized that the athero-protective effects of LXR ligands could be in part mediated through platelets and therefore explored the potential role of LXR in platelets. Our results show that LXR-β is present in human platelets and the LXR ligands, GW3965 and T0901317, modulated nongenomically platelet aggregation stimulated by a range of agonists. GW3965 caused LXR to associate with signaling components proximal to the collagen receptor, GPVI, suggesting a potential mechanism of LXR action in platelets that leads to diminished platelet responses. Activation of platelets at sites of atherosclerotic lesions results in thrombosis preceding myocardial infarction and stroke. Using an in vivo model of thrombosis in mice, we show that GW3965 has antithrombotic effects, reducing the size and the stability of thrombi. The athero-protective effects of GW3965, together with its novel antiplatelet/thrombotic effects, indicate LXR as a potential target for prevention of athero-thrombotic disease.</abstract><cop>Washington, DC</cop><pub>Elsevier Inc</pub><pmid>21411760</pmid><doi>10.1182/blood-2010-09-306142</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0006-4971 |
| ispartof | Blood, 2011-05, Vol.117 (21), p.5751-5761 |
| issn | 0006-4971 1528-0020 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3110032 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Animals Atherosclerosis - complications Benzoates - therapeutic use Benzylamines - therapeutic use Biological and medical sciences Calcium - metabolism Flow Cytometry Hematologic and hematopoietic diseases Humans Hydrocarbons, Fluorinated - therapeutic use Immunoblotting Immunoprecipitation Ligands Liver X Receptors Medical sciences Mice Mice, Inbred C57BL Orphan Nuclear Receptors - metabolism Platelet Aggregation - drug effects Platelet Glycoprotein GPIIb-IIIa Complex - metabolism Platelet Membrane Glycoproteins - metabolism Sulfonamides - therapeutic use Thrombosis - etiology Thrombosis - prevention & control Thrombosis and Hemostasis |
| title | LXR as a novel antithrombotic target |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-21T05%3A24%3A06IST&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=LXR%20as%20a%20novel%20antithrombotic%20target&rft.jtitle=Blood&rft.au=Spyridon,%20Michael&rft.date=2011-05-26&rft.volume=117&rft.issue=21&rft.spage=5751&rft.epage=5761&rft.pages=5751-5761&rft.issn=0006-4971&rft.eissn=1528-0020&rft_id=info:doi/10.1182/blood-2010-09-306142&rft_dat=%3Cproquest_pubme%3E869000187%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=869000187&rft_id=info:pmid/21411760&rft_els_id=S0006497120450517&rfr_iscdi=true |