Pravastatin in vivo reduces mononuclear cell migration through endothelial monolayers.
The objective was to evaluate pravastatin modulation on peripheral blood mononuclear cell (PBMC) migration across endothelial monolayers. Eleven hypercholesterolaemic patients were treated with pravastatin 20 mg/day. At baseline (T0), after 40 days (T40) and after 6 months (T 6 months) of treatment total serum cholesterol, low-density lipoprotein (LDL), high-density lipoprotein, triglycerides, C-reactive protein, as well as tumour necrosis factor-alpha (TNF-alpha) and metalloproteinases-9 plasma levels were evaluated. At the same time points the effect of pravastatin on migration of PBMCs through a monolayer of murine brain endothelial cells was studied both in basal conditions and after endothelial stimulation with recombinant mouse TNF-alpha 10 ng/ml for 24 h. Seven volunteers were used as healthy controls. Significant decreases in total cholesterol, LDL and triglycerides as well as inhibition of transmigration were observed. PBMCs transmigration in patients prior to pravastatin therapy was higher than in healthy controls. These results suggest that pravastatin could be of benefit in a spectrum of diseases characterised by extravasation of PBMCs into the central nervous system.
Frigerio
S
S
National Neurological Institute C. Besta, Via Celoria 11, I-20133, Milan, Italy.
Gelati
M
M
Boncoraglio
G
G
Ciusani
E
E
Croci
D
D
de Curtis
M
M
Parati
E
E
Salmaggi
A
A
D000368:Aged; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects*; D004727:Endothelium / Q000187:drug effects / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy / Q000473:pathology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000502:physiology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D017035:Pravastatin / Q000494:pharmacology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000924:Anticholesteremic Agents; D014409:Tumor Necrosis Factor-alpha; D020780:Matrix Metalloproteinase 9; D017035:Pravastatin