iloprost and Hyperlipoproteinemia-Type-II

Topics: Epoprostenol; Humans; Hyperlipoproteinemia Type II; Hyperlipoproteinemias; Iloprost; In Vitro Techniques; Platelet Aggregation

The effect of lowering total serum cholesterol and low-density lipoprotein (LDL) cholesterol on platelet function, thromboxane formation and platelet sensitivity against PGI2 was studied in platelet-rich plasma ex vivo. Additionally, PGI2 receptors were determined in membrane preparations of these platelets. Twelve patients suffering from familial hyperlipoproteinemia type IIa (FH) were treated for 8 months with simvastatin (20-40 mg/day) and compared with 10 untreated FH patients and 10 untreated normocholesterolemic subjects. Compared with those of healthy controls, platelets of untreated FH patients were hyperreactive, as shown by an enhanced aggregation response and release of ATP and thromboxane after stimulation by collagen (0.3-5 micrograms/ml) and ADP (0.3-10 micrograms/ml). Simvastatin reduced the total and LDL serum cholesterol towards control levels while HDL cholesterol remained unchanged. This was accompanied by a significant decrease of platelet aggregation, thromboxane formation and ATP secretion being no more different from normocholesterolemic controls. In addition, the reduced platelet sensitivity against prostacyclin (aggregation, stimulation of cAMP formation) in untreated FH patients was improved to normal values by simvastatin. This was associated with a significant elevation of the reduced prostacyclin binding sites and might be explained by an improved access of prostacyclin to its receptors at platelet membranes. These data demonstrate that the reduction of total and LDL serum cholesterol by simvastatin results in a normalization of platelet function by (i) reduction of platelet hyperreactivity and (ii) improvement of the sensitivity against prostacyclin towards normal via enhanced PGI2-binding sites.

Topics: Adenosine Triphosphate; Adult; Aged; Anticholesteremic Agents; Blood Platelets; Cyclic AMP; Epoprostenol; Humans; Hyperlipoproteinemia Type II; Iloprost; Lipids; Lovastatin; Middle Aged; Platelet Aggregation; Receptors, Epoprostenol; Receptors, Prostaglandin; Simvastatin; Thromboxane B2

The effect of lowering total plasma and low density lipoprotein (LDL) cholesterol in heterozygous familial hypercholesterolaemia type IIa (FH) on platelet function, thromboxane (TX) formation and platelet sensitivity against iloprost, a stable prostacyclin mimetic, was studied in platelet-rich plasma ex vivo. Seven FH patients were treated with cholestyramine (12 g day 1) for 8-11 months and were compared with eight untreated FH patients and 11 healthy control subjects. In comparison with platelets from healthy controls, platelets from untreated FH patients exhibited a significantly increased aggregation response and TX formation, and a reduced reactivity against inhibition of platelet aggregation by prostacyclin. Treatment with cholestyramine for 8-11 months resulted in a 21% reduction in total serum and LDL-cholesterol. This was not accompanied by any change in platelet hyperreactivity or TX formation. However, cholestyramine treatment normalized the platelet reactivity of FH patients against iloprost, being no more different from healthy controls. It is concluded that reduction in plasma cholesterol by cholestyramine results in normalization of the reduced platelet sensitivity against prostacyclin. This might contribute to beneficial effects of cholestyramine treatment in preventing thromboembolic complications of atherosclerosis.

Topics: Blood Platelets; Cardiovascular Agents; Cholestyramine Resin; Epoprostenol; Humans; Hyperlipoproteinemia Type II; Iloprost; Male; Platelet Aggregation; Thromboxane B2