[Pleiotropic effects of micronized fenofibrate in patients with combined hyperlipidemia].
More and more recent studies demonstrate the pleiotropic effects of fibrates. Except lowering plasma lipid levels they can influence blood coagulation abnormalities and stabilise atherosclerotic lesions--a frequent result of the activation of inflammatory cells within the vascular wall. The anti-inflammatory action of fibrates includes inhibiting the release of many cytokines, such as Tumor Necrosis Factor e (TNF-alpha) by these cells. The aim of this study was to evaluate the effect of fenofibrate on the plasma levels of Plasminogen Activator Inhibitor type 1 (PAI-1) and fibrinogen in patients with combined dyslipidemia. Moreover, we assessed the amount of TNF-alpha released by peripheral blood isolated monocytes before and after therapy. Fourteen patients (8 women and 6 men) with hyperlipidemia IIb were treated with micronized fenofibrate (Lipanthyl 200 m, Fournier) in a daily dose of 200 mg for one month. The control group consisted of 12 individuals matched for age with biochemical confirmation of normolipemia. Plasma PAI-1 and TNF-alpha levels were measured by the ELISA method. Fibrinogen levels were measured according to the commonly used Clauss method. Before treatment the haemostatic compounds and TNF-alpha studied were significantly higher in the group with hyperlipidaemia IIb compared to the control group. One-month therapy with fenofibrate resulted in significant decrease of triglycerides and total cholesterol. After treatment, PAI-1 and fibrinogen levels also decreased significantly: PAI-1 from 101.18 +/- 9.74 ng/mL to 81.22 +/- 6.68 ng/mL, p < 0.01 and fibrinogen from 364.5 +/- 29.6 mg/dL to 294.7 +/- 19.3 mg/dL, p < 0.01. The study also revealed that the level of produced TNF-alpha decreased significantly from 2136.0 +/- 250.8 pg/mL to 1336.8 +/- 132.0 pg/mL, p < 0.05. These results may confirm new pathways of fibrates action.
Okopień
Bogusław
B
Zakład Farmakologii Klinicznej Katedry Farmakologii SI. AM, Katowicach.
Cwalina
Łukasz
Ł
Haberka
Maciej
M
Kowalski
Jan
J
Zieliński
Marek
M
Szwed
Zygmunt
Z
Kalina
Zbigniew
Z
Herman
Zbigniew S
ZS
D000328:Adult; D002352:Carrier Proteins / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy* / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D016896:Treatment Outcome; D014280:Triglycerides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D002352:Carrier Proteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D016207:Cytokines; D000960:Hypolipidemic Agents; D017395:Plasminogen Activator Inhibitor 1; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; C066845:pleiotrophin; D010959:Tissue Plasminogen Activator; D011345:Fenofibrate