thromboxane-a2 and Hyperlipoproteinemia-Type-II

Platelet phospholipid composition was analyzed before and after extracorporeal removal of low density lipoproteins (LDL) by LDL apheresis in six patients with familial hypercholesterolemia. Elevated levels of total plasma cholesterol and the portion of plasma cholesterol carried by LDL were reduced by 56 and 66% after LDL apheresis. Platelet cholesterol contents remained unaffected. While the phosphatidylcholine (PC):sphingomyelin (SM) ratio in plasma lipoproteins was increased by 22% following apheresis, the same parameter was lowered by 14% in platelets. LDL apheresis induced decreases in the percentages of distinct molecular species containing arachidonic acid in platelet diacyl subgroups of PC, phosphatidylinositol (PI) and phosphatidylserine (PS) as well as in alkenylacyl (plasmalogen) phosphatidylethanolamine (PE). Directly after apheresis, the percentages of molecular species with arachidonic acid of diacyl PC, diacyl PI and alkenylacyl PE were reduced by 20, 23 and 8%, respectively. Two days after the procedure, total arachidonic acid of diacyl PC, diacyl PS and alkenylacyl PE was lowered by 11, 20 and 8%. Overall, the amount of phospholipid bound arachidonic acid was reduced by 16% after apheresis (from 79.1 to 66.4 nmol/10(8) platelets). The results are thus in agreement with previous data indicating decreased phospholipid bound arachidonic acid in red blood cells after apheresis (Engelman B. Bräutigam C, Kulschar R et al. Biochim Biophys Acta 1994:1196:154). Urinary 2,3-dinor thromboxane B2, an estimate of platelet thromboxane A2 (TXA2) production, tended to be decreased following the procedure. The percentage change in the TXA2 metabolite was positively related to the magnitude of change induced by apheresis in phospholipid bound arachidonic acid. In summary, the results suggest that in patients with hypercholesterolemia, the level of plasma LDL is an important determinant of the arachidonic acid content of several platelet phospholipids.

Topics: Adult; Arachidonic Acid; Blood Component Removal; Blood Platelets; Humans; Hyperlipoproteinemia Type II; Immunosorbent Techniques; Lipoproteins, LDL; Male; Middle Aged; Phospholipids; Thromboxane A2; Thromboxane B2

Platelets from familial hypercholesterolaemia type IIa patients are hyperreactive and produce increased amounts of thromboxane A2. These modifications of platelet function may play an important role in the occurrence of premature atherosclerosis. One approach to the prevention of the thromboembolic complications of atherosclerosis is the use of antiplatelet agents which depress platelet function. Ridogrel, a combined thromboxane synthase inhibitor and thromboxane A2/prostaglandin endoperoxide receptor blocker inhibits platelet aggregation. This study was designed to investigate the in vitro effect of ridogrel on platelet function in normocholesterolaemic and familial hypercholesterolaemia type IIa subjects. In citrated platelet rich plasma ridogrel significantly inhibited platelet aggregation and thromboxane A2 production in response to collagen, ADP and arachidonic acid stimulation. In washed platelets ridogrel significantly decreased aggregation and serotonin release. Ridogrel significantly increased cAMP levels in response to thrombin stimulation. In conclusion, ridogrel at low concentrations significantly inhibited the in vitro function of platelets in a dose dependant manner in both normocholesterolaemic subjects and familial hypercholesterolaemia IIa subjects.

Topics: Adult; Blood Platelets; Enzyme Inhibitors; Humans; Hyperlipoproteinemia Type II; In Vitro Techniques; Middle Aged; Pentanoic Acids; Platelet Aggregation Inhibitors; Pyridines; Thromboxane A2; Thromboxane B2; Thromboxane-A Synthase

Platelets from patients with familial hypercholesterolemia (type IIa hyperlipoproteinemia), a condition associated with high prevalence of atherosclerosis and of its thrombotic complications, are known to be hyperresponsive to aggregating stimuli and to synthesize increased amounts of thromboxane A2 (TxA2) in comparison to platelets from normal subjects. In order to search if these functional alterations are linked to a different platelet lipid composition, we studied a group of young patients affected by IIa hyperlipoproteinemia and a group of suitable controls with similar dietary habits. Both cholesterol and phospholipid content of platelets were higher in patients than in controls with a significant increase of cholesterol/phospholipid molar ratio (at least p less than 0.05). The percent contents of the main platelet phospholipid fractions were not altered, while an increase in saturated fatty acids, both unesterified and esterified in different lipid fractions, was observed. Moreover, an increased TxA2 production by platelets and a significantly increased number of megathrombocytes occur in patients with respect to controls (p less than 0.001). Our results indicates that platelets from patients with IIa hyperlipoproteinemia have an altered lipid composition which could explain, at least in part, the enhanced platelet reactivity reported in these patients.

Topics: Adult; Blood Platelets; Erythrocytes; Female; Humans; Hyperlipoproteinemia Type II; Lipids; Male; Platelet Count; Thromboxane A2

Topics: Adenosine Diphosphate; Animals; Blood Platelets; Blood Vessels; Coronary Disease; Diet; Disease Models, Animal; Endothelium; Fatty Acids; Humans; Hyperlipoproteinemia Type II; Lipids; Lipoproteins, HDL; Lipoproteins, LDL; Thrombosis; Thromboxane A2

Topics: Blood Platelets; Cell Membrane; Cholesterol; Humans; Hyperlipoproteinemia Type II; Phospholipids; Platelet Aggregation; Thromboxane A2