Free fatty acids trigger apoptosis and inhibit cell cycle progression in human vascular endothelial cells
ABSTRACT Plasma free fatty acid (FFA) concentrations are increased in states of insulin resistance and impair endothelial function. Because the underlying mechanisms are largely unknown, we examined selected, purified FFAs' (100–300 µmol/l, 24–48 h) action on apoptosis, cell cycle distribution,...
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| Veröffentlicht in: | The FASEB journal 2004-01, Vol.18 (1), p.146-148 |
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| creator | Artwohl, Michaela Roden, Michael Waldhäusl, Werner Freudenthaler, Angelika Baumgartner‐Parzer, Sabina M. |
| description | ABSTRACT
Plasma free fatty acid (FFA) concentrations are increased in states of insulin resistance and impair endothelial function. Because the underlying mechanisms are largely unknown, we examined selected, purified FFAs' (100–300 µmol/l, 24–48 h) action on apoptosis, cell cycle distribution, and associated gene/protein expression in human umbilical vein endothelial cells (HUVECs). Stearic acid, but not oleic acid, time and concentration dependently increased endothelial apoptosis by fivefold (n=6, P |
| doi_str_mv | 10.1096/fj.03-0301fje |
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Plasma free fatty acid (FFA) concentrations are increased in states of insulin resistance and impair endothelial function. Because the underlying mechanisms are largely unknown, we examined selected, purified FFAs' (100–300 µmol/l, 24–48 h) action on apoptosis, cell cycle distribution, and associated gene/protein expression in human umbilical vein endothelial cells (HUVECs). Stearic acid, but not oleic acid, time and concentration dependently increased endothelial apoptosis by fivefold (n=6, P<0.01), whereas polyunsaturated FFAs (PUFAs; linoleic, γ‐linolenic, and arachidonic acid) exerted proapoptotic activity only at 300 µmol/l (P<0.05). Proapoptotic FFA action increased with FFAs' number of double bonds and with protein expression of the apoptosis promotor bak. The G0/G1 cell cycle arrest (n=6, P<0.05) induced by stearic acid (+14%) and PUFAs (+30%) is reflected by up‐regulation of p21WAF‐1/Cip1. In addition, all FFAs concentration dependently reduced (P<0.05) gene/protein expression of clusterin (–54%), NF‐κB's inhibitor, IκBα (–50%), endothelin‐1 (–44%), and endothelial NO synthase (–44%). Plasma samples obtained from individuals with elevated plasma FFAs (372±22 µmol/l) increased endothelial apoptosis by 4.2‐fold (P<0.001, n=10) compared with intraindividually matched low plasma FFA (56±21 µmol/l) conditions, underlining the results obtained by defined FFA stimulation. In conclusion, FFA structure differently affects endothelial cell proliferation and apoptosis, both representing key factors in the development of micro‐ and macrovascular dysfunction.</description><identifier>ISSN: 0892-6638</identifier><identifier>EISSN: 1530-6860</identifier><identifier>DOI: 10.1096/fj.03-0301fje</identifier><identifier>PMID: 14597560</identifier><language>eng</language><publisher>United States: Federation of American Societies for Experimental Biology</publisher><subject>Apoptosis ; bcl-2 Homologous Antagonist-Killer Protein ; Cell Cycle - drug effects ; Cells, Cultured ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclins - metabolism ; diabetes ; endothelial dysfunction ; Endothelium, Vascular - cytology ; Endothelium, Vascular - drug effects ; Endothelium, Vascular - metabolism ; Fatty Acids, Nonesterified - pharmacology ; Humans ; Linoleic Acids, Conjugated - pharmacology ; Membrane Proteins - metabolism ; vascular complications</subject><ispartof>The FASEB journal, 2004-01, Vol.18 (1), p.146-148</ispartof><rights>FASEB</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c406E-906c586dd69773674160c898e086f95c9729ff1431594d7c0a0c92cd7227db543</citedby><cites>FETCH-LOGICAL-c406E-906c586dd69773674160c898e086f95c9729ff1431594d7c0a0c92cd7227db543</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1096%2Ffj.03-0301fje$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1096%2Ffj.03-0301fje$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14597560$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Artwohl, Michaela</creatorcontrib><creatorcontrib>Roden, Michael</creatorcontrib><creatorcontrib>Waldhäusl, Werner</creatorcontrib><creatorcontrib>Freudenthaler, Angelika</creatorcontrib><creatorcontrib>Baumgartner‐Parzer, Sabina M.</creatorcontrib><title>Free fatty acids trigger apoptosis and inhibit cell cycle progression in human vascular endothelial cells</title><title>The FASEB journal</title><addtitle>FASEB J</addtitle><description>ABSTRACT
Plasma free fatty acid (FFA) concentrations are increased in states of insulin resistance and impair endothelial function. Because the underlying mechanisms are largely unknown, we examined selected, purified FFAs' (100–300 µmol/l, 24–48 h) action on apoptosis, cell cycle distribution, and associated gene/protein expression in human umbilical vein endothelial cells (HUVECs). Stearic acid, but not oleic acid, time and concentration dependently increased endothelial apoptosis by fivefold (n=6, P<0.01), whereas polyunsaturated FFAs (PUFAs; linoleic, γ‐linolenic, and arachidonic acid) exerted proapoptotic activity only at 300 µmol/l (P<0.05). Proapoptotic FFA action increased with FFAs' number of double bonds and with protein expression of the apoptosis promotor bak. The G0/G1 cell cycle arrest (n=6, P<0.05) induced by stearic acid (+14%) and PUFAs (+30%) is reflected by up‐regulation of p21WAF‐1/Cip1. In addition, all FFAs concentration dependently reduced (P<0.05) gene/protein expression of clusterin (–54%), NF‐κB's inhibitor, IκBα (–50%), endothelin‐1 (–44%), and endothelial NO synthase (–44%). Plasma samples obtained from individuals with elevated plasma FFAs (372±22 µmol/l) increased endothelial apoptosis by 4.2‐fold (P<0.001, n=10) compared with intraindividually matched low plasma FFA (56±21 µmol/l) conditions, underlining the results obtained by defined FFA stimulation. In conclusion, FFA structure differently affects endothelial cell proliferation and apoptosis, both representing key factors in the development of micro‐ and macrovascular dysfunction.</description><subject>Apoptosis</subject><subject>bcl-2 Homologous Antagonist-Killer Protein</subject><subject>Cell Cycle - drug effects</subject><subject>Cells, Cultured</subject><subject>Cyclin-Dependent Kinase Inhibitor p21</subject><subject>Cyclins - metabolism</subject><subject>diabetes</subject><subject>endothelial dysfunction</subject><subject>Endothelium, Vascular - cytology</subject><subject>Endothelium, Vascular - drug effects</subject><subject>Endothelium, Vascular - metabolism</subject><subject>Fatty Acids, Nonesterified - pharmacology</subject><subject>Humans</subject><subject>Linoleic Acids, Conjugated - pharmacology</subject><subject>Membrane Proteins - metabolism</subject><subject>vascular complications</subject><issn>0892-6638</issn><issn>1530-6860</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kL1PwzAUxC0EoqUwsiJPbCnPceLYbFA1QFWJAZgt1x-tqzQpdgLqf09KK7ExPZ3e706nQ-iawJiAYHduPQaaAAXi1vYEDUlOIWGcwSkaAhdpwhjlA3QR4xoACBB2jgYky0WRMxgiXwZrsVNtu8NKexNxG_xyaQNW22bbNtFHrGqDfb3yC99ibasK652uLN6GZhlsjL6p-zdedRtV4y8VdVepgG1tmnZlK6-qX1O8RGdOVdFeHe8IfZTT98lzMn99epk8zBOdAZsmApjOOTOGiaKgrMgIA80Ft8CZE7kWRSqcIxkluchMoUGBFqk2RZoWZpFndIRuD7l9v8_OxlZufNw3ULVtuig5AOdMsB5MDqAOTYzBOrkNfqPCThKQ-22lW0ug8rhtz98cg7vFxpo_-jhmD9wfgG9f2d3_abJ8e0zLWa96Xc6m9Aeveofa</recordid><startdate>200401</startdate><enddate>200401</enddate><creator>Artwohl, Michaela</creator><creator>Roden, Michael</creator><creator>Waldhäusl, Werner</creator><creator>Freudenthaler, Angelika</creator><creator>Baumgartner‐Parzer, Sabina M.</creator><general>Federation of American Societies for Experimental Biology</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><scope>7X8</scope></search><sort><creationdate>200401</creationdate><title>Free fatty acids trigger apoptosis and inhibit cell cycle progression in human vascular endothelial cells</title><author>Artwohl, Michaela ; Roden, Michael ; Waldhäusl, Werner ; Freudenthaler, Angelika ; Baumgartner‐Parzer, Sabina M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c406E-906c586dd69773674160c898e086f95c9729ff1431594d7c0a0c92cd7227db543</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Apoptosis</topic><topic>bcl-2 Homologous Antagonist-Killer Protein</topic><topic>Cell Cycle - drug effects</topic><topic>Cells, Cultured</topic><topic>Cyclin-Dependent Kinase Inhibitor p21</topic><topic>Cyclins - metabolism</topic><topic>diabetes</topic><topic>endothelial dysfunction</topic><topic>Endothelium, Vascular - cytology</topic><topic>Endothelium, Vascular - drug effects</topic><topic>Endothelium, Vascular - metabolism</topic><topic>Fatty Acids, Nonesterified - pharmacology</topic><topic>Humans</topic><topic>Linoleic Acids, Conjugated - pharmacology</topic><topic>Membrane Proteins - metabolism</topic><topic>vascular complications</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Artwohl, Michaela</creatorcontrib><creatorcontrib>Roden, Michael</creatorcontrib><creatorcontrib>Waldhäusl, Werner</creatorcontrib><creatorcontrib>Freudenthaler, Angelika</creatorcontrib><creatorcontrib>Baumgartner‐Parzer, Sabina M.</creatorcontrib><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>The FASEB journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Artwohl, Michaela</au><au>Roden, Michael</au><au>Waldhäusl, Werner</au><au>Freudenthaler, Angelika</au><au>Baumgartner‐Parzer, Sabina M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Free fatty acids trigger apoptosis and inhibit cell cycle progression in human vascular endothelial cells</atitle><jtitle>The FASEB journal</jtitle><addtitle>FASEB J</addtitle><date>2004-01</date><risdate>2004</risdate><volume>18</volume><issue>1</issue><spage>146</spage><epage>148</epage><pages>146-148</pages><issn>0892-6638</issn><eissn>1530-6860</eissn><abstract>ABSTRACT
Plasma free fatty acid (FFA) concentrations are increased in states of insulin resistance and impair endothelial function. Because the underlying mechanisms are largely unknown, we examined selected, purified FFAs' (100–300 µmol/l, 24–48 h) action on apoptosis, cell cycle distribution, and associated gene/protein expression in human umbilical vein endothelial cells (HUVECs). Stearic acid, but not oleic acid, time and concentration dependently increased endothelial apoptosis by fivefold (n=6, P<0.01), whereas polyunsaturated FFAs (PUFAs; linoleic, γ‐linolenic, and arachidonic acid) exerted proapoptotic activity only at 300 µmol/l (P<0.05). Proapoptotic FFA action increased with FFAs' number of double bonds and with protein expression of the apoptosis promotor bak. The G0/G1 cell cycle arrest (n=6, P<0.05) induced by stearic acid (+14%) and PUFAs (+30%) is reflected by up‐regulation of p21WAF‐1/Cip1. In addition, all FFAs concentration dependently reduced (P<0.05) gene/protein expression of clusterin (–54%), NF‐κB's inhibitor, IκBα (–50%), endothelin‐1 (–44%), and endothelial NO synthase (–44%). Plasma samples obtained from individuals with elevated plasma FFAs (372±22 µmol/l) increased endothelial apoptosis by 4.2‐fold (P<0.001, n=10) compared with intraindividually matched low plasma FFA (56±21 µmol/l) conditions, underlining the results obtained by defined FFA stimulation. In conclusion, FFA structure differently affects endothelial cell proliferation and apoptosis, both representing key factors in the development of micro‐ and macrovascular dysfunction.</abstract><cop>United States</cop><pub>Federation of American Societies for Experimental Biology</pub><pmid>14597560</pmid><doi>10.1096/fj.03-0301fje</doi><tpages>21</tpages></addata></record> |
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| subjects | Apoptosis bcl-2 Homologous Antagonist-Killer Protein Cell Cycle - drug effects Cells, Cultured Cyclin-Dependent Kinase Inhibitor p21 Cyclins - metabolism diabetes endothelial dysfunction Endothelium, Vascular - cytology Endothelium, Vascular - drug effects Endothelium, Vascular - metabolism Fatty Acids, Nonesterified - pharmacology Humans Linoleic Acids, Conjugated - pharmacology Membrane Proteins - metabolism vascular complications |
| title | Free fatty acids trigger apoptosis and inhibit cell cycle progression in human vascular endothelial cells |
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