title: In vitro and in vivo effects of statins on platelet-activating factor and its metabolism.
abstract: Platelet activating factor (PAF) is implicated in cardiovascular disease (CVD). Statins are widely used in these situations. Therefore, we assessed their effect on the biological activities and metabolism of PAF. Several statins, including simvastatin, exhibited an inhibitory effect against PAF, comparable with that of PAF-inhibitors. Simvastatin also suppressed in vivo PAF-biosynthesis via the de novo pathway, in leukocytes of 6 simvastatin-treated volunteers. Total cholesterol and low-density lipoprotein cholesterol were also significantly decreased, whereas high-density lipoprotein cholesterol, triacylglycerol, EC(50), and lag time were unaffected in these participants. Simvastatin with an intact lactone ring also inhibited PAF-activities, while incubation of human mesangial cells with it also resulted in decreased de novo PAF-biosynthesis. This suggests that these simvastatin-dependent effects are independent of its lactone ring. These new actions of statins should be further studied in PAF-implicated pathological conditions such as CVD, cancer, and renal disease.
authors.affiliation: Laboratory of Biochemistry, Faculty of Chemistry, National and Kapodistrian University, Athens, Greece.
authors.forename: Nektaria
authors.initials: N
authors.lastname: Tsantila
authors.forename: Alexandros B
authors.initials: AB
authors.lastname: Tsoupras
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Fragopoulou
authors.forename: Smaragdi
authors.initials: S
authors.lastname: Antonopoulou
authors.forename: Christos
authors.initials: C
authors.lastname: Iatrou
authors.forename: Constantinos A
authors.initials: CA
authors.lastname: Demopoulos
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008297:Male; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism; D010972:Platelet Activating Factor / Q000378:metabolism*; D011817:Rabbits; D015203:Reproducibility of Results; D019821:Simvastatin / Q000494:pharmacology*; D018709:Statistics, Nonparametric
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010972:Platelet Activating Factor; D019821:Simvastatin