title: Ciprofibrate increases plasma concentration of platelet-derived growth factor AB in patients with advanced atherosclerosis and hyperlipidemia independently of its hypolipidemic effects.
abstract: Fibrates, besides their hypolipidemic action, share alternative effects, such as decreased plasma fibrinogen and uric acid levels. Because of their complex action, additional effects have been investigated. A group of 23 patients with clinical signs of atherosclerosis and hyperlipoproteinemia was randomly allocated after a 1-month washout period and treated with either 100 mg/d of ciprofibrate or 100 mg/d of aspirin for 2 months. Patients were then treated with a combination of these two agents for the next 2 months. Ciprofibrate decreased plasma concentrations of triglycerides (-29%) and very-low-density lipoprotein cholesterol (-27%) in monotherapy and a larger reduction was observed if ciprofibrate was added to the aspirin therapy: triglycerides (-39%), very-low-density lipoprotein cholesterol (-33%), total cholesterol (-18%), low-density lipoprotein cholesterol (-17%), and increased high-density lipoprotein cholesterol (+36%). Ciprofibrate increased plasma levels of platelet-derived growth factor (PDGF) AB in both monotherapy patients (+162.9 pg/ml, +297%) and in aspirin-pretreated patients (+129.8 pg/ml, +134%); the increase of PDGF AB platelet store was significant only in aspirin-pretreated patients (+11.1 ng/ml, +51%). Aspirin in monotherapy did not modulate either plasma or platelet store of PDGF AB. Ciprofibrate did not inhibit thromboxane B 2 synthesis in platelets. Aspirin did not influence plasma thromboxane B 2 concentration at all, whereas it decreased thromboxane B 2 platelet production markedly in monotherapy (-85%) and in combination with ciprofibrate (-91%). Ciprofibrate increases PDGF AB content, which is amplified by aspirin pretreatment without correlation with its hypolipidemic action. The increase of PDGF production is suggested to participate in plaque stabilization.
authors.affiliation: Institute of Preventive and Clinical Medicine, Department of Pharmacotherapy, Bratislava, Slovak Republic. gajdos@upkm.sl
authors.forename: M
authors.initials: M
authors.lastname: Gajdos
authors.forename: V
authors.initials: V
authors.lastname: Mongiellová
authors.forename: D
authors.initials: D
authors.lastname: Huttová
authors.forename: L
authors.initials: L
authors.lastname: Cibulová
authors.forename: Z
authors.initials: Z
authors.lastname: Krivosíková
authors.forename: V
authors.initials: V
authors.lastname: Spustová
authors.forename: R
authors.initials: R
authors.lastname: Dzúrik
mesh_terms: D000368:Aged; D001161:Arteriosclerosis / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use; D002995:Clofibric Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D058607:Fibric Acids; D005340:Fibrinogen / Q000032:analysis; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D010976:Platelet Count; D010982:Platelet-Derived Growth Factor / Q000032:analysis*
chemical_list: D058607:Fibric Acids; D005343:Fibrinolytic Agents; D000960:Hypolipidemic Agents; D010975:Platelet Aggregation Inhibitors; D010982:Platelet-Derived Growth Factor; D002995:Clofibric Acid; D005340:Fibrinogen; C019304:ciprofibrate; D001241:Aspirin