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Serum Heat Shock Protein 27 Levels Represent a Potential Therapeutic Target for Atherosclerosis: Observations From a Human Cohort and Treatment of Female Mice
The aim of this study was to evaluate the potential of serum heat shock protein 27 (HSP27) as a therapeutic target in coronary artery disease. Expression of HSP27 in human coronary arteries diminishes with the progression of atherosclerosis, whereas ubiquitous HSP27 overexpression in apolipoprotein...
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| Published in: | Journal of the American College of Cardiology 2013-10, Vol.62 (16), p.1446-1454 |
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| Main Authors: | , , , , , , , , , , , , |
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| container_title | Journal of the American College of Cardiology |
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| creator | SEIBERT, Tara A HIBBERT, Benjamin HAWKEN, Steven WILSON, Kumanan R O'BRIEN, Edward R CHEN, Yong-Xiang RAYNER, Katey SIMARD, Trevor TIEQIANG HU CUERRIER, Charles M XIAOLING ZHAO DE BELLEROCHE, Jacqueline CHOW, Benjamin J. W |
| description | The aim of this study was to evaluate the potential of serum heat shock protein 27 (HSP27) as a therapeutic target in coronary artery disease.
Expression of HSP27 in human coronary arteries diminishes with the progression of atherosclerosis, whereas ubiquitous HSP27 overexpression in apolipoprotein E(-/-) (ApoE(-/-)) mice attenuates atherogenesis. However, it remains unclear whether increasing serum HSP27 levels alone is sufficient for atheroprotection.
Low- and intermediate-risk patients undergoing coronary or computed tomography angiography had serum HSP27 levels measured. Elevated serum HSP27 levels in female atheroprone ApoE(-/-) mice were achieved by transplantation with HSP27 overexpressing bone marrow or by administering recombinant HSP27.
Patients with >50% stenosis in any major epicardial artery had lower HSP27 levels compared with those free of atherosclerosis (median [interquartile range]: 2,176 pg/ml [551-5,475] vs. 6,200 pg/ml [2,575-9,560]; p < 0.001). After a 5-year period of clinical follow-up, low serum HSP27 levels ( |
| doi_str_mv | 10.1016/j.jacc.2013.05.041 |
| format | article |
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Expression of HSP27 in human coronary arteries diminishes with the progression of atherosclerosis, whereas ubiquitous HSP27 overexpression in apolipoprotein E(-/-) (ApoE(-/-)) mice attenuates atherogenesis. However, it remains unclear whether increasing serum HSP27 levels alone is sufficient for atheroprotection.
Low- and intermediate-risk patients undergoing coronary or computed tomography angiography had serum HSP27 levels measured. Elevated serum HSP27 levels in female atheroprone ApoE(-/-) mice were achieved by transplantation with HSP27 overexpressing bone marrow or by administering recombinant HSP27.
Patients with >50% stenosis in any major epicardial artery had lower HSP27 levels compared with those free of atherosclerosis (median [interquartile range]: 2,176 pg/ml [551-5,475] vs. 6,200 pg/ml [2,575-9,560]; p < 0.001). After a 5-year period of clinical follow-up, low serum HSP27 levels (<50th percentile) were predictive of subsequent major adverse cardiovascular events (hazard ratio: 2.93, 95% confidence interval: 1.06 to 8.12; p = 0.04). In experimental murine models of atherosclerosis, increasing serum HSP27 levels both reduced de novo atherosclerotic lesion formation and enhanced features of plaque stability.
In humans, low serum HSP27 levels are associated with the presence of coronary artery disease and prognostic of future adverse clinical events. In mouse models of atherosclerosis, increasing HSP27 levels reduced lesion progression and promoted features of plaque stability. Serum HSP27 levels may represent a potential therapeutic target for atherosclerosis.</description><identifier>ISSN: 0735-1097</identifier><identifier>EISSN: 1558-3597</identifier><identifier>DOI: 10.1016/j.jacc.2013.05.041</identifier><identifier>PMID: 23764828</identifier><identifier>CODEN: JACCDI</identifier><language>eng</language><publisher>New York, NY: Elsevier</publisher><subject>Aged ; Animals ; Atherosclerosis (general aspects, experimental research) ; Atherosclerosis - blood ; Atherosclerosis - diagnosis ; Atherosclerosis - drug therapy ; Atherosclerosis - physiopathology ; Biological and medical sciences ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Cohort Studies ; Coronary Angiography - methods ; Coronary Vessels - pathology ; Disease Models, Animal ; Female ; Heart ; HSP27 Heat-Shock Proteins - blood ; HSP27 Heat-Shock Proteins - pharmacology ; Humans ; Male ; Medical sciences ; Mice ; Middle Aged ; Multidetector Computed Tomography - methods ; Outcome Assessment (Health Care) ; Plaque, Atherosclerotic - drug therapy ; Plaque, Atherosclerotic - pathology ; Plaque, Atherosclerotic - physiopathology ; Predictive Value of Tests ; Prognosis ; Treatment Outcome</subject><ispartof>Journal of the American College of Cardiology, 2013-10, Vol.62 (16), p.1446-1454</ispartof><rights>2015 INIST-CNRS</rights><rights>Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28032169$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23764828$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>SEIBERT, Tara A</creatorcontrib><creatorcontrib>HIBBERT, Benjamin</creatorcontrib><creatorcontrib>HAWKEN, Steven</creatorcontrib><creatorcontrib>WILSON, Kumanan R</creatorcontrib><creatorcontrib>O'BRIEN, Edward R</creatorcontrib><creatorcontrib>CHEN, Yong-Xiang</creatorcontrib><creatorcontrib>RAYNER, Katey</creatorcontrib><creatorcontrib>SIMARD, Trevor</creatorcontrib><creatorcontrib>TIEQIANG HU</creatorcontrib><creatorcontrib>CUERRIER, Charles M</creatorcontrib><creatorcontrib>XIAOLING ZHAO</creatorcontrib><creatorcontrib>DE BELLEROCHE, Jacqueline</creatorcontrib><creatorcontrib>CHOW, Benjamin J. W</creatorcontrib><title>Serum Heat Shock Protein 27 Levels Represent a Potential Therapeutic Target for Atherosclerosis: Observations From a Human Cohort and Treatment of Female Mice</title><title>Journal of the American College of Cardiology</title><addtitle>J Am Coll Cardiol</addtitle><description>The aim of this study was to evaluate the potential of serum heat shock protein 27 (HSP27) as a therapeutic target in coronary artery disease.
Expression of HSP27 in human coronary arteries diminishes with the progression of atherosclerosis, whereas ubiquitous HSP27 overexpression in apolipoprotein E(-/-) (ApoE(-/-)) mice attenuates atherogenesis. However, it remains unclear whether increasing serum HSP27 levels alone is sufficient for atheroprotection.
Low- and intermediate-risk patients undergoing coronary or computed tomography angiography had serum HSP27 levels measured. Elevated serum HSP27 levels in female atheroprone ApoE(-/-) mice were achieved by transplantation with HSP27 overexpressing bone marrow or by administering recombinant HSP27.
Patients with >50% stenosis in any major epicardial artery had lower HSP27 levels compared with those free of atherosclerosis (median [interquartile range]: 2,176 pg/ml [551-5,475] vs. 6,200 pg/ml [2,575-9,560]; p < 0.001). After a 5-year period of clinical follow-up, low serum HSP27 levels (<50th percentile) were predictive of subsequent major adverse cardiovascular events (hazard ratio: 2.93, 95% confidence interval: 1.06 to 8.12; p = 0.04). In experimental murine models of atherosclerosis, increasing serum HSP27 levels both reduced de novo atherosclerotic lesion formation and enhanced features of plaque stability.
In humans, low serum HSP27 levels are associated with the presence of coronary artery disease and prognostic of future adverse clinical events. In mouse models of atherosclerosis, increasing HSP27 levels reduced lesion progression and promoted features of plaque stability. Serum HSP27 levels may represent a potential therapeutic target for atherosclerosis.</description><subject>Aged</subject><subject>Animals</subject><subject>Atherosclerosis (general aspects, experimental research)</subject><subject>Atherosclerosis - blood</subject><subject>Atherosclerosis - diagnosis</subject><subject>Atherosclerosis - drug therapy</subject><subject>Atherosclerosis - physiopathology</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Cardiology. Vascular system</subject><subject>Cohort Studies</subject><subject>Coronary Angiography - methods</subject><subject>Coronary Vessels - pathology</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Heart</subject><subject>HSP27 Heat-Shock Proteins - blood</subject><subject>HSP27 Heat-Shock Proteins - pharmacology</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Middle Aged</subject><subject>Multidetector Computed Tomography - methods</subject><subject>Outcome Assessment (Health Care)</subject><subject>Plaque, Atherosclerotic - drug therapy</subject><subject>Plaque, Atherosclerotic - pathology</subject><subject>Plaque, Atherosclerotic - physiopathology</subject><subject>Predictive Value of Tests</subject><subject>Prognosis</subject><subject>Treatment Outcome</subject><issn>0735-1097</issn><issn>1558-3597</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNpFkE1v00AQhlcIREPLH-CA5oLExWY__cGtighBCmrVpudovB6TDbbX7K4r8Wf6W3FFEJcZad5Hz4yGsXeC54KL4tMpP6G1ueRC5dzkXIsXbCWMqTJl6vIlW_FSmUzwurxgb2I8cc6LStSv2YVUZaErWa3Y0z2FeYAtYYL7o7c_4Tb4RG4EWcKOHqmPcEdToEhjAoTbJRyTwx72Rwo40ZychT2GH5Sg8wGu0zL30fbP1cXPcNNECo-YnB8jbIIfFst2HnCEtT_6sEjHFvZhOWB4XuE72NCAPcF3Z-mKveqwj_T23C_Zw-bLfr3Ndjdfv62vd9kktUiZMaJVupGFtFZzpEZ0llA2baM0YU2Gl1hUNeemXAiqdV1RIaltEYVobKcu2ce_3in4XzPFdBhctNT3OJKf40ForTTnqjAL-v6Mzs1A7WEKbsDw-_Dvpwvw4QxgtNh3AUfr4n-u4kqKolZ_AHVxiTw</recordid><startdate>20131015</startdate><enddate>20131015</enddate><creator>SEIBERT, Tara A</creator><creator>HIBBERT, Benjamin</creator><creator>HAWKEN, Steven</creator><creator>WILSON, Kumanan R</creator><creator>O'BRIEN, Edward R</creator><creator>CHEN, Yong-Xiang</creator><creator>RAYNER, Katey</creator><creator>SIMARD, Trevor</creator><creator>TIEQIANG HU</creator><creator>CUERRIER, Charles M</creator><creator>XIAOLING ZHAO</creator><creator>DE BELLEROCHE, Jacqueline</creator><creator>CHOW, Benjamin J. 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Vascular system</topic><topic>Cohort Studies</topic><topic>Coronary Angiography - methods</topic><topic>Coronary Vessels - pathology</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>Heart</topic><topic>HSP27 Heat-Shock Proteins - blood</topic><topic>HSP27 Heat-Shock Proteins - pharmacology</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Middle Aged</topic><topic>Multidetector Computed Tomography - methods</topic><topic>Outcome Assessment (Health Care)</topic><topic>Plaque, Atherosclerotic - drug therapy</topic><topic>Plaque, Atherosclerotic - pathology</topic><topic>Plaque, Atherosclerotic - physiopathology</topic><topic>Predictive Value of Tests</topic><topic>Prognosis</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SEIBERT, Tara A</creatorcontrib><creatorcontrib>HIBBERT, Benjamin</creatorcontrib><creatorcontrib>HAWKEN, Steven</creatorcontrib><creatorcontrib>WILSON, Kumanan R</creatorcontrib><creatorcontrib>O'BRIEN, Edward R</creatorcontrib><creatorcontrib>CHEN, Yong-Xiang</creatorcontrib><creatorcontrib>RAYNER, Katey</creatorcontrib><creatorcontrib>SIMARD, Trevor</creatorcontrib><creatorcontrib>TIEQIANG HU</creatorcontrib><creatorcontrib>CUERRIER, Charles M</creatorcontrib><creatorcontrib>XIAOLING ZHAO</creatorcontrib><creatorcontrib>DE BELLEROCHE, Jacqueline</creatorcontrib><creatorcontrib>CHOW, Benjamin J. W</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>MEDLINE - Academic</collection><jtitle>Journal of the American College of Cardiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>SEIBERT, Tara A</au><au>HIBBERT, Benjamin</au><au>HAWKEN, Steven</au><au>WILSON, Kumanan R</au><au>O'BRIEN, Edward R</au><au>CHEN, Yong-Xiang</au><au>RAYNER, Katey</au><au>SIMARD, Trevor</au><au>TIEQIANG HU</au><au>CUERRIER, Charles M</au><au>XIAOLING ZHAO</au><au>DE BELLEROCHE, Jacqueline</au><au>CHOW, Benjamin J. W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Serum Heat Shock Protein 27 Levels Represent a Potential Therapeutic Target for Atherosclerosis: Observations From a Human Cohort and Treatment of Female Mice</atitle><jtitle>Journal of the American College of Cardiology</jtitle><addtitle>J Am Coll Cardiol</addtitle><date>2013-10-15</date><risdate>2013</risdate><volume>62</volume><issue>16</issue><spage>1446</spage><epage>1454</epage><pages>1446-1454</pages><issn>0735-1097</issn><eissn>1558-3597</eissn><coden>JACCDI</coden><abstract>The aim of this study was to evaluate the potential of serum heat shock protein 27 (HSP27) as a therapeutic target in coronary artery disease.
Expression of HSP27 in human coronary arteries diminishes with the progression of atherosclerosis, whereas ubiquitous HSP27 overexpression in apolipoprotein E(-/-) (ApoE(-/-)) mice attenuates atherogenesis. However, it remains unclear whether increasing serum HSP27 levels alone is sufficient for atheroprotection.
Low- and intermediate-risk patients undergoing coronary or computed tomography angiography had serum HSP27 levels measured. Elevated serum HSP27 levels in female atheroprone ApoE(-/-) mice were achieved by transplantation with HSP27 overexpressing bone marrow or by administering recombinant HSP27.
Patients with >50% stenosis in any major epicardial artery had lower HSP27 levels compared with those free of atherosclerosis (median [interquartile range]: 2,176 pg/ml [551-5,475] vs. 6,200 pg/ml [2,575-9,560]; p < 0.001). After a 5-year period of clinical follow-up, low serum HSP27 levels (<50th percentile) were predictive of subsequent major adverse cardiovascular events (hazard ratio: 2.93, 95% confidence interval: 1.06 to 8.12; p = 0.04). In experimental murine models of atherosclerosis, increasing serum HSP27 levels both reduced de novo atherosclerotic lesion formation and enhanced features of plaque stability.
In humans, low serum HSP27 levels are associated with the presence of coronary artery disease and prognostic of future adverse clinical events. In mouse models of atherosclerosis, increasing HSP27 levels reduced lesion progression and promoted features of plaque stability. Serum HSP27 levels may represent a potential therapeutic target for atherosclerosis.</abstract><cop>New York, NY</cop><pub>Elsevier</pub><pmid>23764828</pmid><doi>10.1016/j.jacc.2013.05.041</doi><tpages>9</tpages></addata></record> |
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| ispartof | Journal of the American College of Cardiology, 2013-10, Vol.62 (16), p.1446-1454 |
| issn | 0735-1097 1558-3597 |
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| source | BACON - Elsevier - GLOBAL_SCIENCEDIRECT-OPENACCESS |
| subjects | Aged Animals Atherosclerosis (general aspects, experimental research) Atherosclerosis - blood Atherosclerosis - diagnosis Atherosclerosis - drug therapy Atherosclerosis - physiopathology Biological and medical sciences Blood and lymphatic vessels Cardiology. Vascular system Cohort Studies Coronary Angiography - methods Coronary Vessels - pathology Disease Models, Animal Female Heart HSP27 Heat-Shock Proteins - blood HSP27 Heat-Shock Proteins - pharmacology Humans Male Medical sciences Mice Middle Aged Multidetector Computed Tomography - methods Outcome Assessment (Health Care) Plaque, Atherosclerotic - drug therapy Plaque, Atherosclerotic - pathology Plaque, Atherosclerotic - physiopathology Predictive Value of Tests Prognosis Treatment Outcome |
| title | Serum Heat Shock Protein 27 Levels Represent a Potential Therapeutic Target for Atherosclerosis: Observations From a Human Cohort and Treatment of Female Mice |
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