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_5 label "Selventa" provenance.
_4 value "Atherosclerosis is a chronic immuno-inflammatory disease involving the recruitment of monocyte and T lymphocytes. Statins (HMG CoA reductase inhibitors) have proven their beneficial effects on reducing total and low-density lipoprotein (LDL) cholesterol. Recent in vitro and in vivo studies have suggested that statins also have anti-inflammatory properties beyond their lipid lowering effects, involving isoprenoid intermediates such as farnesylpyrophosphate (FPP) and geranylgeranylpyrophosphate (GGPP). Chemokines and their receptors are known to induce leukocytes migration, and recently have been implicated in atherogenesis. To investigate whether statins could reduce the expression of chemokines and chemokine/receptors expression in vivo, we used male LDLR-/- mice fed with a high-cholesterol diet treated or not with pravastatin (10 mg/kg/d) through drinking water. We demonstrate here that the expression of the chemokines RANTES, MCP-1 and IP-10 as well as the chemokine/receptors CCR1, CCR2 and CCR5 were downregulated within atherosclerotic vascular tissue in the statin-treated mice compared to controls. To confirm these findings, we performed in vitro experiments on vascular human smooth muscle cells and endothelial cells. Western Blot, ELISA and RPAs revealed that statins markedly decreased chemokines and chemokine/receptors expression. These effects could be reversed by mevalonate, GGPP and FPP. Inhibition of the GGPP prenylation pathway by GTI confirmed that synthesis of chemokines and their receptors might be mainly Rho dependent. These in vitro and in vivo results clearly indicate that statins have anti-inflammatory properties beyond their lipid effects, which might help to better understand their great clinical benefice in preventing cardiovascular diseases." provenance.
_4 wasQuotedFrom _3 provenance.
assertion hadPrimarySource _3 provenance.
large_corpus.bel title "BEL Framework Large Corpus Document" provenance.
_3 title "AHA Abstracts 84" 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 84" provenance.
_3 type "Other" provenance.