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All rights reserved. http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/title BEL Framework Large Corpus Document http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/authoredBy http://www.tkuhn.ch/bel2nanopub/RAQs4mPruaiwCZZg25Qr_Dcw-SomHXn0ZmHyPFdJ9vihE#_4 http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/version 1.4 http://www.tkuhn.ch/bel2nanopub/RAQs4mPruaiwCZZg25Qr_Dcw-SomHXn0ZmHyPFdJ9vihE#_2 http://purl.org/dc/elements/1.1/identifier AHA Abstracts P316 http://www.tkuhn.ch/bel2nanopub/RAQs4mPruaiwCZZg25Qr_Dcw-SomHXn0ZmHyPFdJ9vihE#_2 http://purl.org/dc/elements/1.1/title AHA Abstracts P316 http://www.tkuhn.ch/bel2nanopub/RAQs4mPruaiwCZZg25Qr_Dcw-SomHXn0ZmHyPFdJ9vihE#_2 http://purl.org/dc/elements/1.1/type Other http://www.tkuhn.ch/bel2nanopub/RAQs4mPruaiwCZZg25Qr_Dcw-SomHXn0ZmHyPFdJ9vihE#_3 http://www.w3.org/ns/prov#value Cell death by apoptosis is recognized as a significant event influencing the development and stability of the atherosclerotic lesion. Evidence suggests that the predominant cell type undergoing apoptosis in formed lesions is the macrophage. HMG-CoA reductase inhibitors (statins) have been previously reported to induce apoptosis in several cell types. Their extensive use in the treatment of hypercholesterolemia therefore justifies the examination of the effects of statins on macrophages. Incubation of thioglycollate-elicited mouse peritoneal macrophages (Tg-MPM) with simvastatin (10 ?M) leads to an induction of apoptosis, as measured by DNA fragmentation, cell morphology changes and phosphatidylserine externalization. Simvastatin- induced apoptosis is accompanied by specific induction of caveolin-1 expression, as assessed by immunoblotting. Simvastatin exposure has no significant effect on caveolin-2 expression. The statin- induced caveolin-1 expression is dose- and time- dependent, with a 20- fold induction in macrophages treated with 10 ?M simvastatin for 72 hrs. Increased caveolin-1 expression is at least partially the result of increased caveolin-1 mRNA levels, as simvastatin treatment increases caveolin-1 mRNA 2- fold. Addition of mevalonate (100 ?M) completely prevents the simvastatin- induced apoptosis as well as increase in caveolin-1. Because the simvastatin- mediated increase in caveolin-1 expression correlates with the degree of apoptosis, we also examined caveolin expression in macrophages deprived of glucose or treated with ethanol. Both treatments induced macrophage apoptosis in a time dependent manner with a concomitant and specific increase in caveolin-1 expression. In conclusion, our data suggest that increased caveolin-1 expression in macrophages undergoing apoptosis is not specific to simvastatin action but rather to induction of apoptosis. This suggests that caveolin and cholesterol-rich membrane domains such as caveolae/lipid rafts may be of general importance in the activation of the apoptotic cascade and influence the extent of macrophage apoptosis in the lesion area. http://www.tkuhn.ch/bel2nanopub/RAQs4mPruaiwCZZg25Qr_Dcw-SomHXn0ZmHyPFdJ9vihE#_3 http://www.w3.org/ns/prov#wasQuotedFrom http://www.tkuhn.ch/bel2nanopub/RAQs4mPruaiwCZZg25Qr_Dcw-SomHXn0ZmHyPFdJ9vihE#_2 http://www.tkuhn.ch/bel2nanopub/RAQs4mPruaiwCZZg25Qr_Dcw-SomHXn0ZmHyPFdJ9vihE#_4 http://www.w3.org/2000/01/rdf-schema#label Selventa http://www.tkuhn.ch/bel2nanopub/RAQs4mPruaiwCZZg25Qr_Dcw-SomHXn0ZmHyPFdJ9vihE#assertion http://www.w3.org/ns/prov#hadPrimarySource http://www.tkuhn.ch/bel2nanopub/RAQs4mPruaiwCZZg25Qr_Dcw-SomHXn0ZmHyPFdJ9vihE#_2 http://www.tkuhn.ch/bel2nanopub/RAQs4mPruaiwCZZg25Qr_Dcw-SomHXn0ZmHyPFdJ9vihE#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://www.tkuhn.ch/bel2nanopub/RAQs4mPruaiwCZZg25Qr_Dcw-SomHXn0ZmHyPFdJ9vihE#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://www.tkuhn.ch/bel2nanopub/RAQs4mPruaiwCZZg25Qr_Dcw-SomHXn0ZmHyPFdJ9vihE#_3 http://www.tkuhn.ch/bel2nanopub/RAQs4mPruaiwCZZg25Qr_Dcw-SomHXn0ZmHyPFdJ9vihE#pubinfo http://www.tkuhn.ch/bel2nanopub/RAQs4mPruaiwCZZg25Qr_Dcw-SomHXn0ZmHyPFdJ9vihE http://purl.org/dc/terms/created 2014-07-03T14:29:45.370+02:00 http://www.tkuhn.ch/bel2nanopub/RAQs4mPruaiwCZZg25Qr_Dcw-SomHXn0ZmHyPFdJ9vihE http://purl.org/pav/createdBy http://orcid.org/0000-0001-6818-334X http://www.tkuhn.ch/bel2nanopub/RAQs4mPruaiwCZZg25Qr_Dcw-SomHXn0ZmHyPFdJ9vihE http://purl.org/pav/createdBy http://orcid.org/0000-0002-1267-0234