Platelet noradrenaline release in patients with familial hypercholesterolaemia

Abstract

We have examined resting and thrombin (0.3 units ml-1) induced release of noradrenaline by washed platelets from 15 normal subjects and eight patients with heterozygous familial hypercholesterolaemia. Platelets from both normal and hypercholesterolaemic subjects showed irreversible aggregation with 0.3 units ml-1 thrombin. Extents of aggregation were 76.3% and 90.8% respectively, platelets from hypercholesterolaemic patients being significantly more sensitive (P less than 0.002). Under resting conditions platelet noradrenaline release was 136% greater (P less than 0.02) in hypercholesterolaemic patients than in normal subjects. Thrombin-stimulated release of noradrenaline was also higher (73%, P less than 0.05) in hypercholesterolaemics than in normals. The differences between resting and thrombin-stimulated release were greater for hypercholesterolaemic patients than normal subjects (P less than 0.05). Under resting conditions total platelet noradrenaline levels (sum of supernatant and platelet pellet concentrations) were similar in preparations from the two groups. However, following thrombin stimulation total noradrenaline concentrations were substantially greater (86%) in platelets from hypercholesterolaemics than normals (P less than 0.02). In hypercholesterolaemic patients thrombin stimulation was associated with an 101% increase (over resting levels) in total platelet noradrenaline (P less than 0.01), no increases being observed with normal subjects. We suggest that platelet membranes may be more permeable in patients with familial hypercholesterolaemia leading to increased non-specific release of catecholamines. Platelets from patients with familial hypercholesterolaemia may also be more responsive to stimulation with respect to catecholamine release. The results obtained on calculation of total platelet noradrenaline levels may indicate that abnormalities of platelet dense granules occur in familial hypercholesterolaemia. In this context the relative proportions of free and conjugated catecholamine may be of relevance.