High-density lipoprotein-associated sphingosine-1-phosphate activity in heterozygous familial hypercholesterolaemia

Patients with heterozygous familial hypercholesterolaemia (FH) suffer from high plasma cholesterol and an environment of increased oxidative stress. We examined its potential effects on high-density lipoprotein (HDL)-associated sphingosine-1-phosphate (S1P) content (HDL-S1P) and HDL-mediated protection against oxidative stress, both with and without statin treatment.

In a case-control study, HDL was isolated from 12 FH patients with and without statin treatment and from 12 healthy controls. The HDL-S1P content and the capacity of HDL to protect cardiomyocytes against oxidative stress in vitro were measured.

HDL-associated S1P was significantly correlated with cell protection, but not with HDL-cholesterol or apolipoprotein AI. The latter did not correlate with HDL-mediated cell protection. Neither the HDL-S1P content nor HDL protective capacity differed between nontreated FH patients and controls. The relative amounts of apolipoprotein AI and apolipoprotein M were similar between controls and FH patients. Statin treatment had no effect on any of these measures.

The FH environment is not detrimental to HDL-S1P content or HDL-S1P-mediated cell protection. Statin treatment does not modulate HDL function in this regard.