Elevated interleukin 8 and matrix metalloproteinase 9 levels are associated with myocardial pathology in users of anabolic-androgenic steroids
Abstract Aims In the current paper, we aim to explore the effect of both current and former long-term anabolic-androgenic steroid (AAS) use on regulation of systemic inflammatory markers and mediators of extracellular matrix (ECM) remodelling and their association with hormones and echocardiographic...
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| Veröffentlicht in: | European journal of preventive cardiology 2024-09, Vol.31 (12), p.1469-1476 |
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| creator | Gregersen, Ida Scarth, Morgan Elizabeth Abdullah, Rang Thorsby, Per Medbøe Hauger, Lisa E Haugaa, Kristina H Sagen, Ellen Lund Michelsen, Annika E Ueland, Thor Edvardsen, Thor Aukrust, Pål Almaas, Vibeke Marie Bjørnebekk, Astrid Kristine Halvorsen, Bente |
| description | Abstract
Aims
In the current paper, we aim to explore the effect of both current and former long-term anabolic-androgenic steroid (AAS) use on regulation of systemic inflammatory markers and mediators of extracellular matrix (ECM) remodelling and their association with hormones and echocardiographic myocardial pathology in weightlifters.
Methods and results
In a cross-sectional study, 93 weightlifting AAS users, of whom 62 were current and 31 were past users, with at least 1-year cumulative AAS use (mean 11 ± 7 accumulated years of AAS use), were compared with 54 non-using weightlifting controls (WLCs) using clinical interview, blood pressure measurements, and echocardiography. Serum levels of interleukin (IL)-6, IL-8, tumour necrosis factor (TNF), interferon (IFN)-γ, growth differentiation factor (GDF)-15, and matrix metalloproteinase (MMP)-9, sex hormones, and lipids were analysed. It was found that serum levels of IL-8, GDF-15, and MMP-9 were significantly increased in current AAS users compared with former users and WLCs. Matrix metalloproteinase 9, but not IL-8, correlated consistently with sex hormone levels, and sex hormone levels correlated consistently with mean wall thickness, in current users. Moreover, HDL cholesterol was significantly lower in current vs. former AAS users and significantly inversely correlated with MMP-9 in current users. Further, in current users, MMP-9 and IL-8 correlated with markers of myocardial strain, and MMP-9 also correlated with indices of cardiac mass, which was not seen in former users. Mediation analyses suggested that MMP-9 could partly explain hormone-induced alterations in markers of myocardial damage in current users.
Conclusion
Long-term AAS is associated with increased levels of markers of inflammation and ECM remodelling, which seems to have a hormone-dependent (MMP-9) and a hormone-independent (IL-8) association with markers of myocardial dysfunction.
Lay Summary
Long-term use of anabolic-androgenic steroids (AASs) can increase inflammation and mediators of extracellular matrix (ECM) remodeling, which potentially could be involved in myocardial pathology seen in individuals using such steroids.Anabolic-androgenic steroid use increased levels of inflammatory marker IL-8 and marker of ECM remodelling matrix metalloproteinase-9 (MMP-9).Interleukin-8 and MMP-9 were both associated with myocardial pathology in current, but not former, users, suggesting that these markers are associated with the risk of myocardi |
| doi_str_mv | 10.1093/eurjpc/zwae126 |
| format | Article |
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Aims
In the current paper, we aim to explore the effect of both current and former long-term anabolic-androgenic steroid (AAS) use on regulation of systemic inflammatory markers and mediators of extracellular matrix (ECM) remodelling and their association with hormones and echocardiographic myocardial pathology in weightlifters.
Methods and results
In a cross-sectional study, 93 weightlifting AAS users, of whom 62 were current and 31 were past users, with at least 1-year cumulative AAS use (mean 11 ± 7 accumulated years of AAS use), were compared with 54 non-using weightlifting controls (WLCs) using clinical interview, blood pressure measurements, and echocardiography. Serum levels of interleukin (IL)-6, IL-8, tumour necrosis factor (TNF), interferon (IFN)-γ, growth differentiation factor (GDF)-15, and matrix metalloproteinase (MMP)-9, sex hormones, and lipids were analysed. It was found that serum levels of IL-8, GDF-15, and MMP-9 were significantly increased in current AAS users compared with former users and WLCs. Matrix metalloproteinase 9, but not IL-8, correlated consistently with sex hormone levels, and sex hormone levels correlated consistently with mean wall thickness, in current users. Moreover, HDL cholesterol was significantly lower in current vs. former AAS users and significantly inversely correlated with MMP-9 in current users. Further, in current users, MMP-9 and IL-8 correlated with markers of myocardial strain, and MMP-9 also correlated with indices of cardiac mass, which was not seen in former users. Mediation analyses suggested that MMP-9 could partly explain hormone-induced alterations in markers of myocardial damage in current users.
Conclusion
Long-term AAS is associated with increased levels of markers of inflammation and ECM remodelling, which seems to have a hormone-dependent (MMP-9) and a hormone-independent (IL-8) association with markers of myocardial dysfunction.
Lay Summary
Long-term use of anabolic-androgenic steroids (AASs) can increase inflammation and mediators of extracellular matrix (ECM) remodeling, which potentially could be involved in myocardial pathology seen in individuals using such steroids.Anabolic-androgenic steroid use increased levels of inflammatory marker IL-8 and marker of ECM remodelling matrix metalloproteinase-9 (MMP-9).Interleukin-8 and MMP-9 were both associated with myocardial pathology in current, but not former, users, suggesting that these markers are associated with the risk of myocardial damage during AAS use.
Graphical Abstract
Graphical Abstract</description><identifier>ISSN: 2047-4873</identifier><identifier>ISSN: 2047-4881</identifier><identifier>EISSN: 2047-4881</identifier><identifier>DOI: 10.1093/eurjpc/zwae126</identifier><identifier>PMID: 38573232</identifier><language>eng</language><publisher>UK: Oxford University Press</publisher><subject>Adult ; Anabolic Agents - adverse effects ; Androgens - blood ; Biomarkers - blood ; Case-Control Studies ; Cross-Sectional Studies ; Female ; Humans ; Inflammation Mediators - blood ; Interleukin-8 - blood ; Male ; Matrix Metalloproteinase 9 - blood ; Middle Aged ; Myocardium - pathology ; Testosterone Congeners - adverse effects ; Testosterone Congeners - blood ; Time Factors ; Up-Regulation</subject><ispartof>European journal of preventive cardiology, 2024-09, Vol.31 (12), p.1469-1476</ispartof><rights>The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. 2024</rights><rights>The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c254t-2a3d824e9dec49de8cbe653c956a58e86cfa7e27f8dca39b23f08b77142c41e53</cites><orcidid>0000-0003-3492-9187 ; 0000-0002-6529-6485 ; 0000-0002-2085-3487 ; 0000-0002-3800-765X ; 0000-0002-9615-1035</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,1584,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38573232$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gregersen, Ida</creatorcontrib><creatorcontrib>Scarth, Morgan Elizabeth</creatorcontrib><creatorcontrib>Abdullah, Rang</creatorcontrib><creatorcontrib>Thorsby, Per Medbøe</creatorcontrib><creatorcontrib>Hauger, Lisa E</creatorcontrib><creatorcontrib>Haugaa, Kristina H</creatorcontrib><creatorcontrib>Sagen, Ellen Lund</creatorcontrib><creatorcontrib>Michelsen, Annika E</creatorcontrib><creatorcontrib>Ueland, Thor</creatorcontrib><creatorcontrib>Edvardsen, Thor</creatorcontrib><creatorcontrib>Aukrust, Pål</creatorcontrib><creatorcontrib>Almaas, Vibeke Marie</creatorcontrib><creatorcontrib>Bjørnebekk, Astrid Kristine</creatorcontrib><creatorcontrib>Halvorsen, Bente</creatorcontrib><title>Elevated interleukin 8 and matrix metalloproteinase 9 levels are associated with myocardial pathology in users of anabolic-androgenic steroids</title><title>European journal of preventive cardiology</title><addtitle>Eur J Prev Cardiol</addtitle><description>Abstract
Aims
In the current paper, we aim to explore the effect of both current and former long-term anabolic-androgenic steroid (AAS) use on regulation of systemic inflammatory markers and mediators of extracellular matrix (ECM) remodelling and their association with hormones and echocardiographic myocardial pathology in weightlifters.
Methods and results
In a cross-sectional study, 93 weightlifting AAS users, of whom 62 were current and 31 were past users, with at least 1-year cumulative AAS use (mean 11 ± 7 accumulated years of AAS use), were compared with 54 non-using weightlifting controls (WLCs) using clinical interview, blood pressure measurements, and echocardiography. Serum levels of interleukin (IL)-6, IL-8, tumour necrosis factor (TNF), interferon (IFN)-γ, growth differentiation factor (GDF)-15, and matrix metalloproteinase (MMP)-9, sex hormones, and lipids were analysed. It was found that serum levels of IL-8, GDF-15, and MMP-9 were significantly increased in current AAS users compared with former users and WLCs. Matrix metalloproteinase 9, but not IL-8, correlated consistently with sex hormone levels, and sex hormone levels correlated consistently with mean wall thickness, in current users. Moreover, HDL cholesterol was significantly lower in current vs. former AAS users and significantly inversely correlated with MMP-9 in current users. Further, in current users, MMP-9 and IL-8 correlated with markers of myocardial strain, and MMP-9 also correlated with indices of cardiac mass, which was not seen in former users. Mediation analyses suggested that MMP-9 could partly explain hormone-induced alterations in markers of myocardial damage in current users.
Conclusion
Long-term AAS is associated with increased levels of markers of inflammation and ECM remodelling, which seems to have a hormone-dependent (MMP-9) and a hormone-independent (IL-8) association with markers of myocardial dysfunction.
Lay Summary
Long-term use of anabolic-androgenic steroids (AASs) can increase inflammation and mediators of extracellular matrix (ECM) remodeling, which potentially could be involved in myocardial pathology seen in individuals using such steroids.Anabolic-androgenic steroid use increased levels of inflammatory marker IL-8 and marker of ECM remodelling matrix metalloproteinase-9 (MMP-9).Interleukin-8 and MMP-9 were both associated with myocardial pathology in current, but not former, users, suggesting that these markers are associated with the risk of myocardial damage during AAS use.
Graphical Abstract
Graphical Abstract</description><subject>Adult</subject><subject>Anabolic Agents - adverse effects</subject><subject>Androgens - blood</subject><subject>Biomarkers - blood</subject><subject>Case-Control Studies</subject><subject>Cross-Sectional Studies</subject><subject>Female</subject><subject>Humans</subject><subject>Inflammation Mediators - blood</subject><subject>Interleukin-8 - blood</subject><subject>Male</subject><subject>Matrix Metalloproteinase 9 - blood</subject><subject>Middle Aged</subject><subject>Myocardium - pathology</subject><subject>Testosterone Congeners - adverse effects</subject><subject>Testosterone Congeners - blood</subject><subject>Time Factors</subject><subject>Up-Regulation</subject><issn>2047-4873</issn><issn>2047-4881</issn><issn>2047-4881</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>TOX</sourceid><sourceid>EIF</sourceid><recordid>eNqFkblOxTAQRS0EAgS0lMglFAEvWZwSITYJiQbqaOJMwODEwXaAx0fwzRjegxYXYxdnzshzCdnn7JizWp7g7J8mffLxBshFuUa2BcurLFeKr_-9K7lF9kJ4YumUTAilNsmWVEUlhRTb5PPc4itE7KgZI3qL87MZqaIwdnSA6M07HTCCtW7yLqIZISCtaWpCGyh4pBCC0-ZH8WbiIx0WToPvDFg6QXx01j0skpzOAX2grk9qaJ01OkszvHvA0Wga0mxnurBLNnqwAfdW9w65vzi_O7vKbm4vr89ObzItijxmAmSnRI51hzpPRekWy0LquiihUKhK3UOFoupVp0HWrZA9U21V8VzonGMhd8jh0pt-9TJjiM1ggkZrYUQ3h0YyKRmruOAJPV6i2rsQPPbN5M0AftFw1nzH0CxjaFYxpIaDlXtuB-z-8N-lJ-BoCbh5-k_2BSrqmBw</recordid><startdate>20240906</startdate><enddate>20240906</enddate><creator>Gregersen, Ida</creator><creator>Scarth, Morgan Elizabeth</creator><creator>Abdullah, Rang</creator><creator>Thorsby, Per Medbøe</creator><creator>Hauger, Lisa E</creator><creator>Haugaa, Kristina H</creator><creator>Sagen, Ellen Lund</creator><creator>Michelsen, Annika E</creator><creator>Ueland, Thor</creator><creator>Edvardsen, Thor</creator><creator>Aukrust, Pål</creator><creator>Almaas, Vibeke Marie</creator><creator>Bjørnebekk, Astrid Kristine</creator><creator>Halvorsen, Bente</creator><general>Oxford University Press</general><scope>TOX</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><orcidid>https://orcid.org/0000-0003-3492-9187</orcidid><orcidid>https://orcid.org/0000-0002-6529-6485</orcidid><orcidid>https://orcid.org/0000-0002-2085-3487</orcidid><orcidid>https://orcid.org/0000-0002-3800-765X</orcidid><orcidid>https://orcid.org/0000-0002-9615-1035</orcidid></search><sort><creationdate>20240906</creationdate><title>Elevated interleukin 8 and matrix metalloproteinase 9 levels are associated with myocardial pathology in users of anabolic-androgenic steroids</title><author>Gregersen, Ida ; Scarth, Morgan Elizabeth ; Abdullah, Rang ; Thorsby, Per Medbøe ; Hauger, Lisa E ; Haugaa, Kristina H ; Sagen, Ellen Lund ; Michelsen, Annika E ; Ueland, Thor ; Edvardsen, Thor ; Aukrust, Pål ; Almaas, Vibeke Marie ; Bjørnebekk, Astrid Kristine ; Halvorsen, Bente</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c254t-2a3d824e9dec49de8cbe653c956a58e86cfa7e27f8dca39b23f08b77142c41e53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adult</topic><topic>Anabolic Agents - adverse effects</topic><topic>Androgens - blood</topic><topic>Biomarkers - blood</topic><topic>Case-Control Studies</topic><topic>Cross-Sectional Studies</topic><topic>Female</topic><topic>Humans</topic><topic>Inflammation Mediators - blood</topic><topic>Interleukin-8 - blood</topic><topic>Male</topic><topic>Matrix Metalloproteinase 9 - blood</topic><topic>Middle Aged</topic><topic>Myocardium - pathology</topic><topic>Testosterone Congeners - adverse effects</topic><topic>Testosterone Congeners - blood</topic><topic>Time Factors</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gregersen, Ida</creatorcontrib><creatorcontrib>Scarth, Morgan Elizabeth</creatorcontrib><creatorcontrib>Abdullah, Rang</creatorcontrib><creatorcontrib>Thorsby, Per Medbøe</creatorcontrib><creatorcontrib>Hauger, Lisa E</creatorcontrib><creatorcontrib>Haugaa, Kristina H</creatorcontrib><creatorcontrib>Sagen, Ellen Lund</creatorcontrib><creatorcontrib>Michelsen, Annika E</creatorcontrib><creatorcontrib>Ueland, Thor</creatorcontrib><creatorcontrib>Edvardsen, Thor</creatorcontrib><creatorcontrib>Aukrust, Pål</creatorcontrib><creatorcontrib>Almaas, Vibeke Marie</creatorcontrib><creatorcontrib>Bjørnebekk, Astrid Kristine</creatorcontrib><creatorcontrib>Halvorsen, Bente</creatorcontrib><collection>Access via Oxford University Press (Open Access Collection)</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 journal of preventive cardiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gregersen, Ida</au><au>Scarth, Morgan Elizabeth</au><au>Abdullah, Rang</au><au>Thorsby, Per Medbøe</au><au>Hauger, Lisa E</au><au>Haugaa, Kristina H</au><au>Sagen, Ellen Lund</au><au>Michelsen, Annika E</au><au>Ueland, Thor</au><au>Edvardsen, Thor</au><au>Aukrust, Pål</au><au>Almaas, Vibeke Marie</au><au>Bjørnebekk, Astrid Kristine</au><au>Halvorsen, Bente</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Elevated interleukin 8 and matrix metalloproteinase 9 levels are associated with myocardial pathology in users of anabolic-androgenic steroids</atitle><jtitle>European journal of preventive cardiology</jtitle><addtitle>Eur J Prev Cardiol</addtitle><date>2024-09-06</date><risdate>2024</risdate><volume>31</volume><issue>12</issue><spage>1469</spage><epage>1476</epage><pages>1469-1476</pages><issn>2047-4873</issn><issn>2047-4881</issn><eissn>2047-4881</eissn><abstract>Abstract
Aims
In the current paper, we aim to explore the effect of both current and former long-term anabolic-androgenic steroid (AAS) use on regulation of systemic inflammatory markers and mediators of extracellular matrix (ECM) remodelling and their association with hormones and echocardiographic myocardial pathology in weightlifters.
Methods and results
In a cross-sectional study, 93 weightlifting AAS users, of whom 62 were current and 31 were past users, with at least 1-year cumulative AAS use (mean 11 ± 7 accumulated years of AAS use), were compared with 54 non-using weightlifting controls (WLCs) using clinical interview, blood pressure measurements, and echocardiography. Serum levels of interleukin (IL)-6, IL-8, tumour necrosis factor (TNF), interferon (IFN)-γ, growth differentiation factor (GDF)-15, and matrix metalloproteinase (MMP)-9, sex hormones, and lipids were analysed. It was found that serum levels of IL-8, GDF-15, and MMP-9 were significantly increased in current AAS users compared with former users and WLCs. Matrix metalloproteinase 9, but not IL-8, correlated consistently with sex hormone levels, and sex hormone levels correlated consistently with mean wall thickness, in current users. Moreover, HDL cholesterol was significantly lower in current vs. former AAS users and significantly inversely correlated with MMP-9 in current users. Further, in current users, MMP-9 and IL-8 correlated with markers of myocardial strain, and MMP-9 also correlated with indices of cardiac mass, which was not seen in former users. Mediation analyses suggested that MMP-9 could partly explain hormone-induced alterations in markers of myocardial damage in current users.
Conclusion
Long-term AAS is associated with increased levels of markers of inflammation and ECM remodelling, which seems to have a hormone-dependent (MMP-9) and a hormone-independent (IL-8) association with markers of myocardial dysfunction.
Lay Summary
Long-term use of anabolic-androgenic steroids (AASs) can increase inflammation and mediators of extracellular matrix (ECM) remodeling, which potentially could be involved in myocardial pathology seen in individuals using such steroids.Anabolic-androgenic steroid use increased levels of inflammatory marker IL-8 and marker of ECM remodelling matrix metalloproteinase-9 (MMP-9).Interleukin-8 and MMP-9 were both associated with myocardial pathology in current, but not former, users, suggesting that these markers are associated with the risk of myocardial damage during AAS use.
Graphical Abstract
Graphical Abstract</abstract><cop>UK</cop><pub>Oxford University Press</pub><pmid>38573232</pmid><doi>10.1093/eurjpc/zwae126</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-3492-9187</orcidid><orcidid>https://orcid.org/0000-0002-6529-6485</orcidid><orcidid>https://orcid.org/0000-0002-2085-3487</orcidid><orcidid>https://orcid.org/0000-0002-3800-765X</orcidid><orcidid>https://orcid.org/0000-0002-9615-1035</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Anabolic Agents - adverse effects Androgens - blood Biomarkers - blood Case-Control Studies Cross-Sectional Studies Female Humans Inflammation Mediators - blood Interleukin-8 - blood Male Matrix Metalloproteinase 9 - blood Middle Aged Myocardium - pathology Testosterone Congeners - adverse effects Testosterone Congeners - blood Time Factors Up-Regulation |
| title | Elevated interleukin 8 and matrix metalloproteinase 9 levels are associated with myocardial pathology in users of anabolic-androgenic steroids |
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