Reverse cholesterol transport in familial hypercholesterolemia.

Purpose Of Review: Familial hypercholesterolemia is characterized by a major elevation in circulating LDL-cholesterol levels, cholesterol deposition within the arterial wall and an increased risk of premature coronary artery disease. The reverse cholesterol transport (RCT) is now considered as a key process that protects against development of atherosclerosis. The major antiatherogenic action of HDL particles is intimately linked to their determinant role in RCT pathway. However, the steady-sate of HDL-cholesterol levels does not represent the optimal marker to evaluate the efficiency of the RCT in all circumstances.

Recent Findings: By using ex-vivo systems for the evaluation of the efficacy of RCT a strong inverse relationship between HDL efflux capacity from macrophages and atherosclerosis progression has been demonstrated. Low HDL-C phenotype observed in familial hypercholesterolemia patients is associated with defective capacities of HDL particles to mediate major steps of the centripetal movement of cholesterol from peripheral cells to feces. However, current available treatment used to reduce LDL-C to therapeutic goals does not correct altered functions of HDL particles in humans.

Summary: In the context of familial hypercholesterolemia, a growing body of evidence suggests that impaired efficacy of the RCT pathway contributes significantly to the progression of atherosclerosis.