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_5 label "Selventa" provenance.
_4 value "Background: Beneficial effects of HMG-CoA reductase inhibitors were initially attributed to the effects on serum cholesterol levels. However, recent evidence suggests that statins may have vascular benefits independent of cholesterol lowering. To determine if statins have direct effects on vascular endothelium, we examined the effects of cerivastatin and pravastatin on tumor necrosis factor (TNF-? and oxidized low density lipoprotein (Ox-LDL)-induced endothelial cell expression of macrophage-colony stimulating factor (M-CSF), a molecule that importantly contributes to the pathogenesis of atherosclerosis. Methods and Results: Human coronary artery endothelial cells (HCAECs) were treated with (TNF)-? (10 ng/ml) or Ox-LDL (100 ?g/ml, thiobarbituric acid reactive substances ranging from 2.6 to 13.4 nmol/mg of LDL protein) in the absence or presence of cerivastatin (1 ?M) and pravastatin (50 ?M). Expression of M-CSF was examined by RNA- and protein- based assays. Both TNF-? and Ox-LDL increased M-CSF mRNA levels (5-fold after 8 hours) and protein levels (4.1-fold induction after 48 hours). Statins downregulated both steady state and TNF-? or Ox-LDL-induced M-CSF mRNA and protein levels in HCAECs. The effects of cerivastatin and pravastatin on M-CSF expression were paralleled by similar changes in M-CSF activity. The reduction of M-CSF activity by cerivastatin and pravastatin was completely reversed by cotreatment of HCAECs with L-mevalonate. In the presence of actinomycin D, cerivastatin and pravastatin both altered the post transcriptional stability of the TNF-? and Ox-LDL-induced M-CSF mRNA. Conclusions: Our studies indicate that inhibition of endothelial HMG-CoA reductase downregulates M-CSF expression predominantly by altering the post-transcriptional stability of M-CSF mRNA. Since M-CSF contributes to the pathogenesis of atherosclerosis, these result suggest a novel mechanism whereby statins, by inhibiting the endothelial cell expression of M-CSF contribute to the anti-inflammatory and anti-atherogenic effects of statins." provenance.
_4 wasQuotedFrom _3 provenance.
assertion hadPrimarySource _3 provenance.
large_corpus.bel title "BEL Framework Large Corpus Document" provenance.
_3 title "AHA Abstracts 1516" provenance.
large_corpus.bel description "Approximately 61,000 statements." provenance.
assertion wasDerivedFrom large_corpus.bel provenance.
assertion wasDerivedFrom _4 provenance.
large_corpus.bel authoredBy _5 provenance.
large_corpus.bel version "20131211" provenance.
_3 identifier "AHA Abstracts 1516" provenance.
_3 type "Other" provenance.