title: Atorvastatin suppresses homocysteine formation in stimulated human peripheral blood mononuclear cells.
abstract: Hyperhomocysteinemia is regarded as an independent risk factor for vascular diseases, and homocysteine is supposed to contribute to oxidative stress and endothelial damage. Statin therapy is an established intervention to reduce the risk of acute events in patients suffering from cardiovascular diseases. Apart from their lipid-lowering capacity, statins also exert anti-inflammatory and antioxidant effects. As cellular immune activation and oxidative stress play a major role in the pathogenesis of cardiovascular diseases, the anti-inflammatory capacity of statins could partly be responsible for the beneficial effects observed in patients. Earlier we reported that stimulated peripheral blood mononuclear cells (PBMCs) release homocysteine. Here we studied the influence of atorvastatin on homocysteine production in stimulated PBMCs and compared changes in cysteine concentrations and in neopterin production, which is a sensitive indicator of cellular immune activation. Stimulation of human PBMCs with the mitogens concanavalin A and phytohemagglutinin induced significant homocysteine and neopterin production compared to unstimulated cells, whereas cysteine concentrations remained unchanged. Treatment of PBMCs with increasing doses of atorvastatin (10-100 microM) suppressed both biochemical pathways in a dose-dependent manner, and cell proliferation was inhibited in parallel. Again, cysteine levels were not influenced by any treatment. The down-regulating effect of atorvastatin on homocysteine formation in vitro indicates that statins may prevent homocysteine accumulation in the blood via immunosuppression.
authors.affiliation: Division of Biological Chemistry, Biocenter, Innsbruck Medical University, and Ludwig Boltzmann Institute of AIDS Research, Innsbruck, Austria.
authors.forename: Katharina
authors.initials: K
authors.lastname: Schroecksnadel
authors.forename: Barbara
authors.initials: B
authors.lastname: Frick
authors.forename: Christiana
authors.initials: C
authors.lastname: Winkler
authors.forename: Barbara
authors.initials: B
authors.lastname: Wirleitner
authors.forename: Günter
authors.initials: G
authors.lastname: Weiss
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fuchs
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000069059:Atorvastatin; D002318:Cardiovascular Diseases / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D003208:Concanavalin A / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006538:Heptanoic Acids / Q000494:pharmacology*; D006711:Homocystine / Q000097:blood*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D019798:Neopterin / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010835:Phytohemagglutinins / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010835:Phytohemagglutinins; D011758:Pyrroles; D003208:Concanavalin A; D006711:Homocystine; D019798:Neopterin; D000069059:Atorvastatin