Adipocyte fatty acid binding protein in atherosclerotic plaques is associated with local vulnerability and is predictive for the occurrence of adverse cardiovascular events
Aims There is an increasing need for translational studies identifying molecular targets contributing to atherosclerotic plaque destabilization. Local molecular plaque markers that are related to plaque vulnerability may hold predictive value to identify patients who are at increased risk to suffer...
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| Veröffentlicht in: | European heart journal 2011-07, Vol.32 (14), p.1758-1768 |
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| creator | Peeters, Wouter de Kleijn, Dominique P.V. Vink, Aryan van de Weg, Sander Schoneveld, Arjan H. Sze, Siu Kwan van der Spek, Peter J. de Vries, Jean-Paul P.M. Moll, Frans L. Pasterkamp, Gerard |
| description | Aims
There is an increasing need for translational studies identifying molecular targets contributing to atherosclerotic plaque destabilization. Local molecular plaque markers that are related to plaque vulnerability may hold predictive value to identify patients who are at increased risk to suffer from cardiovascular events. Animal studies revealed that adipocyte fatty acid binding protein (FABP4) is associated with the progression of atherosclerosis; however, FABP4 expression studies in human atherosclerotic plaques are lacking. We investigated FABP4 expression in carotid atherosclerotic lesions in relation to plaque composition and future cardiovascular events.
Methods and results
Atherosclerotic plaques were obtained from 561 patients undergoing carotid endarterectomy (CEA). Plaques were analysed for the presence of macrophages, lipid core, smooth-muscle cells, collagen, calcification, and intraplaque haemorrhage. Patients were followed for 3 years after CEA. The primary outcome was defined as the composite of vascular death, vascular event, and surgical or percutaneous vascular intervention. Fatty acid binding protein levels correlated with unstable plaque characteristics and symptomatic lesions. Patients with increased FABP4 plaque levels showed a two-fold increased risk [HR = 1.99, 95% confidence interval (95% CI) (1.30-3.04)] (P = 0.005) to reach the primary outcome during follow-up. Increased FABP4 levels related to primary outcome, independent from general cardiovascular risk factors [HR = 1.33, 95% CI (1.08-1.65)] (P = 0.008).
Conclusion
FABP4 levels in atherosclerotic lesions are associated with an unstable plaque phenotype and an increased risk for cardiovascular events during follow-up. Besides risk stratification for adverse future cardiovascular events, the outcome of the present study supports the relevance of exploring FABP4 antagonists as a potential pharmaceutical intervention to treat atherosclerotic disease progression. |
| doi_str_mv | 10.1093/eurheartj/ehq387 |
| format | Article |
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There is an increasing need for translational studies identifying molecular targets contributing to atherosclerotic plaque destabilization. Local molecular plaque markers that are related to plaque vulnerability may hold predictive value to identify patients who are at increased risk to suffer from cardiovascular events. Animal studies revealed that adipocyte fatty acid binding protein (FABP4) is associated with the progression of atherosclerosis; however, FABP4 expression studies in human atherosclerotic plaques are lacking. We investigated FABP4 expression in carotid atherosclerotic lesions in relation to plaque composition and future cardiovascular events.
Methods and results
Atherosclerotic plaques were obtained from 561 patients undergoing carotid endarterectomy (CEA). Plaques were analysed for the presence of macrophages, lipid core, smooth-muscle cells, collagen, calcification, and intraplaque haemorrhage. Patients were followed for 3 years after CEA. The primary outcome was defined as the composite of vascular death, vascular event, and surgical or percutaneous vascular intervention. Fatty acid binding protein levels correlated with unstable plaque characteristics and symptomatic lesions. Patients with increased FABP4 plaque levels showed a two-fold increased risk [HR = 1.99, 95% confidence interval (95% CI) (1.30-3.04)] (P = 0.005) to reach the primary outcome during follow-up. Increased FABP4 levels related to primary outcome, independent from general cardiovascular risk factors [HR = 1.33, 95% CI (1.08-1.65)] (P = 0.008).
Conclusion
FABP4 levels in atherosclerotic lesions are associated with an unstable plaque phenotype and an increased risk for cardiovascular events during follow-up. Besides risk stratification for adverse future cardiovascular events, the outcome of the present study supports the relevance of exploring FABP4 antagonists as a potential pharmaceutical intervention to treat atherosclerotic disease progression.</description><identifier>ISSN: 0195-668X</identifier><identifier>EISSN: 1522-9645</identifier><identifier>DOI: 10.1093/eurheartj/ehq387</identifier><identifier>PMID: 21059735</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Atherosclerosis (general aspects, experimental research) ; Biological and medical sciences ; Biomarkers - metabolism ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Carotid Artery Diseases - blood ; Carotid Artery Diseases - mortality ; Carotid Artery Diseases - pathology ; Death, Sudden, Cardiac - etiology ; Disease Progression ; Fatty Acid-Binding Proteins - metabolism ; Female ; Humans ; Immunohistochemistry ; Male ; Medical sciences ; Middle Aged ; Myocardial Infarction - mortality ; Plaque, Atherosclerotic - blood ; Plaque, Atherosclerotic - mortality ; Plaque, Atherosclerotic - pathology ; Prognosis ; Stroke - mortality</subject><ispartof>European heart journal, 2011-07, Vol.32 (14), p.1758-1768</ispartof><rights>Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2010. For permissions please email: journals.permissions@oxfordjournals.org 2010</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c406t-81fd50f4c4f22fd115b244d73151da50b8dd2dc367cea1051a659d527834d5a43</citedby><cites>FETCH-LOGICAL-c406t-81fd50f4c4f22fd115b244d73151da50b8dd2dc367cea1051a659d527834d5a43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,1584,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24317662$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21059735$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Peeters, Wouter</creatorcontrib><creatorcontrib>de Kleijn, Dominique P.V.</creatorcontrib><creatorcontrib>Vink, Aryan</creatorcontrib><creatorcontrib>van de Weg, Sander</creatorcontrib><creatorcontrib>Schoneveld, Arjan H.</creatorcontrib><creatorcontrib>Sze, Siu Kwan</creatorcontrib><creatorcontrib>van der Spek, Peter J.</creatorcontrib><creatorcontrib>de Vries, Jean-Paul P.M.</creatorcontrib><creatorcontrib>Moll, Frans L.</creatorcontrib><creatorcontrib>Pasterkamp, Gerard</creatorcontrib><title>Adipocyte fatty acid binding protein in atherosclerotic plaques is associated with local vulnerability and is predictive for the occurrence of adverse cardiovascular events</title><title>European heart journal</title><addtitle>Eur Heart J</addtitle><description>Aims
There is an increasing need for translational studies identifying molecular targets contributing to atherosclerotic plaque destabilization. Local molecular plaque markers that are related to plaque vulnerability may hold predictive value to identify patients who are at increased risk to suffer from cardiovascular events. Animal studies revealed that adipocyte fatty acid binding protein (FABP4) is associated with the progression of atherosclerosis; however, FABP4 expression studies in human atherosclerotic plaques are lacking. We investigated FABP4 expression in carotid atherosclerotic lesions in relation to plaque composition and future cardiovascular events.
Methods and results
Atherosclerotic plaques were obtained from 561 patients undergoing carotid endarterectomy (CEA). Plaques were analysed for the presence of macrophages, lipid core, smooth-muscle cells, collagen, calcification, and intraplaque haemorrhage. Patients were followed for 3 years after CEA. The primary outcome was defined as the composite of vascular death, vascular event, and surgical or percutaneous vascular intervention. Fatty acid binding protein levels correlated with unstable plaque characteristics and symptomatic lesions. Patients with increased FABP4 plaque levels showed a two-fold increased risk [HR = 1.99, 95% confidence interval (95% CI) (1.30-3.04)] (P = 0.005) to reach the primary outcome during follow-up. Increased FABP4 levels related to primary outcome, independent from general cardiovascular risk factors [HR = 1.33, 95% CI (1.08-1.65)] (P = 0.008).
Conclusion
FABP4 levels in atherosclerotic lesions are associated with an unstable plaque phenotype and an increased risk for cardiovascular events during follow-up. Besides risk stratification for adverse future cardiovascular events, the outcome of the present study supports the relevance of exploring FABP4 antagonists as a potential pharmaceutical intervention to treat atherosclerotic disease progression.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Atherosclerosis (general aspects, experimental research)</subject><subject>Biological and medical sciences</subject><subject>Biomarkers - metabolism</subject><subject>Blood and lymphatic vessels</subject><subject>Cardiology. Vascular system</subject><subject>Carotid Artery Diseases - blood</subject><subject>Carotid Artery Diseases - mortality</subject><subject>Carotid Artery Diseases - pathology</subject><subject>Death, Sudden, Cardiac - etiology</subject><subject>Disease Progression</subject><subject>Fatty Acid-Binding Proteins - metabolism</subject><subject>Female</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Myocardial Infarction - mortality</subject><subject>Plaque, Atherosclerotic - blood</subject><subject>Plaque, Atherosclerotic - mortality</subject><subject>Plaque, Atherosclerotic - pathology</subject><subject>Prognosis</subject><subject>Stroke - mortality</subject><issn>0195-668X</issn><issn>1522-9645</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU-L1TAUxYMoznN070qyERdSJ2mTtF0Og_9gwI2Cu3Kb3Pgy5DWdJO3wvpMf0pT3HJdCSLL43XM49xDymrMPnPXNFS5xjxDz3RXu75uufUJ2XNZ11Sshn5Id472slOp-XpAXKd0xxjrF1XNyUXMm-7aRO_L72rg56GNGaiHnIwXtDB3dZNz0i84xZHQTLQfyHmNI2pc7O01nD_cLJuoShZSCdpDR0AeX99QHDZ6ui58wwui822Qns6FzRON0dmuxC5EWTRq0XmLESZevpWBWjAmphmhcWCHpxUOkuOKU00vyzIJP-Or8XpIfnz5-v_lS3X77_PXm-rbSgqlcddwayazQwta1NZzLsRbCtA2X3IBkY2dMbXSjWo1QNsFByd7Iuu0aYSSI5pK8O-mW_FvIPBxc0ug9TBiWNHRtK3jDRV1IdiJ12U2KaIc5ugPE48DZsFU0PFY0nCoqI2_O4st4QPM48LeTArw9AyU9eBth0i7940TDW6U27_cnLizz_23_AKbssaA</recordid><startdate>20110701</startdate><enddate>20110701</enddate><creator>Peeters, Wouter</creator><creator>de Kleijn, Dominique P.V.</creator><creator>Vink, Aryan</creator><creator>van de Weg, Sander</creator><creator>Schoneveld, Arjan H.</creator><creator>Sze, Siu Kwan</creator><creator>van der Spek, Peter J.</creator><creator>de Vries, Jean-Paul P.M.</creator><creator>Moll, Frans L.</creator><creator>Pasterkamp, Gerard</creator><general>Oxford University Press</general><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></search><sort><creationdate>20110701</creationdate><title>Adipocyte fatty acid binding protein in atherosclerotic plaques is associated with local vulnerability and is predictive for the occurrence of adverse cardiovascular events</title><author>Peeters, Wouter ; de Kleijn, Dominique P.V. ; Vink, Aryan ; van de Weg, Sander ; Schoneveld, Arjan H. ; Sze, Siu Kwan ; van der Spek, Peter J. ; de Vries, Jean-Paul P.M. ; Moll, Frans L. ; Pasterkamp, Gerard</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c406t-81fd50f4c4f22fd115b244d73151da50b8dd2dc367cea1051a659d527834d5a43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Atherosclerosis (general aspects, experimental research)</topic><topic>Biological and medical sciences</topic><topic>Biomarkers - metabolism</topic><topic>Blood and lymphatic vessels</topic><topic>Cardiology. Vascular system</topic><topic>Carotid Artery Diseases - blood</topic><topic>Carotid Artery Diseases - mortality</topic><topic>Carotid Artery Diseases - pathology</topic><topic>Death, Sudden, Cardiac - etiology</topic><topic>Disease Progression</topic><topic>Fatty Acid-Binding Proteins - metabolism</topic><topic>Female</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Myocardial Infarction - mortality</topic><topic>Plaque, Atherosclerotic - blood</topic><topic>Plaque, Atherosclerotic - mortality</topic><topic>Plaque, Atherosclerotic - pathology</topic><topic>Prognosis</topic><topic>Stroke - mortality</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Peeters, Wouter</creatorcontrib><creatorcontrib>de Kleijn, Dominique P.V.</creatorcontrib><creatorcontrib>Vink, Aryan</creatorcontrib><creatorcontrib>van de Weg, Sander</creatorcontrib><creatorcontrib>Schoneveld, Arjan H.</creatorcontrib><creatorcontrib>Sze, Siu Kwan</creatorcontrib><creatorcontrib>van der Spek, Peter J.</creatorcontrib><creatorcontrib>de Vries, Jean-Paul P.M.</creatorcontrib><creatorcontrib>Moll, Frans L.</creatorcontrib><creatorcontrib>Pasterkamp, Gerard</creatorcontrib><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><jtitle>European heart journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Peeters, Wouter</au><au>de Kleijn, Dominique P.V.</au><au>Vink, Aryan</au><au>van de Weg, Sander</au><au>Schoneveld, Arjan H.</au><au>Sze, Siu Kwan</au><au>van der Spek, Peter J.</au><au>de Vries, Jean-Paul P.M.</au><au>Moll, Frans L.</au><au>Pasterkamp, Gerard</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Adipocyte fatty acid binding protein in atherosclerotic plaques is associated with local vulnerability and is predictive for the occurrence of adverse cardiovascular events</atitle><jtitle>European heart journal</jtitle><addtitle>Eur Heart J</addtitle><date>2011-07-01</date><risdate>2011</risdate><volume>32</volume><issue>14</issue><spage>1758</spage><epage>1768</epage><pages>1758-1768</pages><issn>0195-668X</issn><eissn>1522-9645</eissn><abstract>Aims
There is an increasing need for translational studies identifying molecular targets contributing to atherosclerotic plaque destabilization. Local molecular plaque markers that are related to plaque vulnerability may hold predictive value to identify patients who are at increased risk to suffer from cardiovascular events. Animal studies revealed that adipocyte fatty acid binding protein (FABP4) is associated with the progression of atherosclerosis; however, FABP4 expression studies in human atherosclerotic plaques are lacking. We investigated FABP4 expression in carotid atherosclerotic lesions in relation to plaque composition and future cardiovascular events.
Methods and results
Atherosclerotic plaques were obtained from 561 patients undergoing carotid endarterectomy (CEA). Plaques were analysed for the presence of macrophages, lipid core, smooth-muscle cells, collagen, calcification, and intraplaque haemorrhage. Patients were followed for 3 years after CEA. The primary outcome was defined as the composite of vascular death, vascular event, and surgical or percutaneous vascular intervention. Fatty acid binding protein levels correlated with unstable plaque characteristics and symptomatic lesions. Patients with increased FABP4 plaque levels showed a two-fold increased risk [HR = 1.99, 95% confidence interval (95% CI) (1.30-3.04)] (P = 0.005) to reach the primary outcome during follow-up. Increased FABP4 levels related to primary outcome, independent from general cardiovascular risk factors [HR = 1.33, 95% CI (1.08-1.65)] (P = 0.008).
Conclusion
FABP4 levels in atherosclerotic lesions are associated with an unstable plaque phenotype and an increased risk for cardiovascular events during follow-up. Besides risk stratification for adverse future cardiovascular events, the outcome of the present study supports the relevance of exploring FABP4 antagonists as a potential pharmaceutical intervention to treat atherosclerotic disease progression.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>21059735</pmid><doi>10.1093/eurheartj/ehq387</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Aged, 80 and over Atherosclerosis (general aspects, experimental research) Biological and medical sciences Biomarkers - metabolism Blood and lymphatic vessels Cardiology. Vascular system Carotid Artery Diseases - blood Carotid Artery Diseases - mortality Carotid Artery Diseases - pathology Death, Sudden, Cardiac - etiology Disease Progression Fatty Acid-Binding Proteins - metabolism Female Humans Immunohistochemistry Male Medical sciences Middle Aged Myocardial Infarction - mortality Plaque, Atherosclerotic - blood Plaque, Atherosclerotic - mortality Plaque, Atherosclerotic - pathology Prognosis Stroke - mortality |
| title | Adipocyte fatty acid binding protein in atherosclerotic plaques is associated with local vulnerability and is predictive for the occurrence of adverse cardiovascular events |
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