Familial hypercholesterolemia (FH) is a genetic disorder characterized by high levels of cholesterol, especially the “bad” cholesterol LDL. In extreme cases, such as in patients who don’t respond to regular medical treatment or suffer from muscle breakdown (rhabdomyolysis) related to the disorder or coronary heart disease, LDL-apheresis is an option. In a process similar to dialysis, a patient’s blood is removed from the body and cleaned of LDL, its subparticles and apolipoproteins, and other molecules involved in liproprotein production before the blood is returned to the patient. The high expense of the procedure has so far restricted its widespread use.
Alexina Orsoni of INSERM and Pierre and Marie Curie University in Paris, tested the efficacy of LDL-apheresis once every two weeks over a minimum of two years in patients with severe FH, comparing pre- and post-LDL-apheresis lipid levels and levels of specific types of HDL that are known to protect against cardiovascular disease. All participants concurrently received the lipid-lowering drugs atorvastatin and ezetimibe. This study, “LDL-apheresis depletes apoE-HDL and pre-beta1-HDL in familial hypercholesterolemia: relevance to atheroprotection,” published in this month’s Journal of Lipid Research, confirmed that LDL-apheresis was successful in significantly lowering total cholesterol, triglyceride and other molecules involved in lipoprotein production, such as apolipoproteins B and E.
Because there are different genes implicated in the development of FH, it was of particular interest that this study showed that LDL-apheresis selectively removed apolipoprotein E-HDL. ApoE-HDL has high electrostatic affinity for the extracellular protein biglycan. Thus, if apoE-HDL exacerbates cholesterol deposition in plaques by binding to biglycan, removal of apoE-HDL2 via apheresis may have an atheroprotective effect.
Mary L. Chang (firstname.lastname@example.org) is managing editor of the Journal of Lipid Research and coordinating journal manager of Molecular and Cellular Proteomics.