thromboplastin and Dyslipidemias

Diabetes is a prothrombotic state involving a more thrombogenic fibrin network. In the present study we investigated the effects of lipid-lowering therapy with atorvastatin on fibrin network structure and platelet-derived microparticles in patients with type 1 diabetes and dyslipidemia.. Twenty patients were treated with atorvastatin (80 mg daily) or placebo during 2 months in a randomized, double-blind, cross-over study. Fibrin network permeability, expression of glycoprotein IIIa, P-selectin and tissue factor on platelet-derived microparticles, plasma endogenous thrombin potential, plasminogen activator inhibitor-1 and tissue plasminogen activator antigen levels were assessed. Additionally, levels of plasma fibrinogen, high-sensitivity C-reactive protein and glycated haemoglobin were measured.. During treatment with atorvastatin, fibrin network permeability increased (p=0.01), while endogenous thrombin potential and expression of glycoprotein IIIa, P-selectin and tissue factor decreased (p<0.01). In vitro experiments indicated that platelet-derived microparticles influence the fibrin network formation as fibrin network permeability decreased significantly when platelet-derived microparticles were added to normal plasma. Baseline levels of plasminogen activator inhibitor-1 and tissue plasminogen activator antigen as well as plasma fibrinogen and high-sensitivity C-reactive protein were within reference values and not significantly changed during atorvastatin treatment, while glycated haemoglobin increased 0.3% (p<0.001).. Novel treatment effects were found in patients with type 1 diabetes and dyslipidemia during atorvastatin therapy, i.e. a more porous fibrin network, to which reduced expression of glycoprotein IIIa, P-selectin and tissue factor on platelet-derived microparticles may contribute. The observed impairment of glycemic control during long-term statin treatment deserves attention.

Topics: Adult; Aged; Atorvastatin; Biomarkers; Blood Platelets; C-Reactive Protein; Cell-Derived Microparticles; Cross-Over Studies; Diabetes Mellitus, Type 1; Double-Blind Method; Dyslipidemias; Fibrin; Fibrinolytic Agents; Glycated Hemoglobin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Integrin beta3; Middle Aged; P-Selectin; Plasminogen Activator Inhibitor 1; Pyrroles; Sweden; Thrombin; Thromboplastin; Thrombosis; Time Factors; Treatment Outcome

Tissue factor (TF) is a key mediator of atherosclerotic plaque thrombogenicity and may be regulated by plaque TF pathway inhibitor (TFPI). High atherogenic lipoproteins are a well-known arterial risk factor, but their effects on the TF/TFPI balance in atherosclerotic plaques, as well as those of widely used lipid-lowering agents such as statins, are incompletely understood.. We analyzed the TF/TFPI balance in carotid plaques from 86 patients, according to the presence of dyslipidemia and statin therapy.. In patients with untreated dyslipidemia (ApoB/ApoA1 ratio >0.7) (D+) (n=44), TF antigen (TF) tended to be higher than in those without dyslipidemia (D-) (n=16). In patients with statins (S+) (n=26), TF was lower than in D+ (p=0.02) and similar to that of D- patients. TFPI antigen was higher in D- than in D+ and S+ patients (p

Topics: Aged; Apolipoprotein A-I; Apolipoproteins B; Carotid Artery Diseases; Case-Control Studies; Cohort Studies; Dyslipidemias; Endarterectomy; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Immunohistochemistry; Lipoproteins; Male; Thromboplastin; Thrombosis