Details

Autor(en) / Beteiligte

• Lambert, Gilles, PhD
• Chatelais, Mathias, BSc
• Petrides, Francine, BSc
• Passard, Maxime, BSc
• Thedrez, Aurélie, PhD
• Rye, Kerry-Anne, PhD
• Schwahn, Uwe, PhD
• Gusarova, Viktoria, PhD
• Blom, Dirk J., MD, PhD
• Sasiela, William, PhD
• Marais, A. David, MD

Titel

Normalization of Low-Density Lipoprotein Receptor Expression in Receptor Defective Homozygous Familial Hypercholesterolemia by Inhibition of PCSK9 With Alirocumab

Ist Teil von

• Journal of the American College of Cardiology, 2014-12, Vol.64 (21), p.2299-2300

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2014

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Proprotein convertase subtilisin kexin type-9 (PCSK9) inhibition using monoclonal antibodies (mAbs) lowers low-density lipoprotein cholesterol (LDL-C) by >50% in heterozygous familial hypercholesterolemia (HeFH) and non-FH dyslipidemic individuals (1). Because PCSK9 is a circulating inhibitor of the LDL receptor (LDLR), PCSK9 inhibition using mAbs should not lower plasma LDL-C in homozygous FH (HoFH) patients who completely lack the receptor (receptor-negative). Human dermal fibroblasts (HDF) isolated from 9 receptor-defective and 4 receptor-negative HoFH patients were grown in 0.5% serum and 40 g/ml mevastatin to maximally up-regulate LDLR, and subsequently incubated with recombinant PCSK9 (either wild-type or the gain of function mutant D374Y) (3), with or without increasing concentrations of alirocumab.