Reduced platelet serotonin content and release in familial hypercholesterolaemia

Plasma and platelet serotonin (5-HT) concentrations, and resting and collagen-induced 5-HT release in platelet-rich plasma were studied in normal and familial hypercholesterolaemic (FH) subjects. Platelet 5-HT concentrations were significantly reduced (-37%, P < 0.01) in FH patients whilst mean plasma concentrations, although increased, were not significantly different from those in normal subjects. Platelet 5-HT correlated negatively with plasma cholesterol when the data for normal subjects and FH, patients were combined (r = -0.48, P = 0.005). It also correlated negatively with low-density lipoprotein (LDL) (FH data, r = -0.59, P = 0.03; normal and FH data, r = -0.49, P = 0.004) but positively with high-density lipoprotein (HDL) (FH r = 0.79, P = 0.001; normal and FH, r = 0.37, P = 0.03). Collagen (5-160 micrograms/ml) stimulated platelet 5-HT release occurred in a concentration-dependent manner. In FH patients stimulated 5-HT release was reduced (10 micrograms/ml collagen, -40%, P < 0.05) and accompanied by increased collagen EC50 values (P < 0.02). Resting 5-HT release was increased substantially in FH patients but not significantly. Our data provide evidence for a relationship between circulating cholesterol and platelet serotonergic mechanisms. It is proposed that abnormalities relating to platelet-plasma 5-HT dynamics, perhaps due to enhanced platelet activity or decreased platelet uptake, may contribute to the cardiovascular complications in FH.