Journal
JOURNAL OF LIPID RESEARCH
Volume 56, Issue 3, Pages 703-712Publisher
ELSEVIER
DOI: 10.1194/jlr.M055665
Keywords
apolipoprotein A-I; reverse cholesterol transport; familial hypoalphalipoproteinemia
Categories
Funding
- Netherlands Heart Foundation [2011-B019]
- Astra Zeneca
- Amgen
- Aegerion
- Biolab
- Boehringer Ingelheim
- Bristol Myers Squibb
- Genzyme
- Pfizer
- Novartis
- Eli Lilly
- Sanofi
- Regeneron
- Unilever
- MSD
- Cerenis
- Torrent
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Reverse cholesterol transport (RCT) contributes to the anti-atherogenic effects of HDL. Patients with the orphan disease, familial hypoalphalipoproteinemia (FHA), are characterized by decreased tissue cholesterol removal and an increased atherogenic burden. We performed an open-label uncontrolled proof-of-concept study to evaluate the effect of infusions with a human apoA-I-containing HDL-mimetic particle (CER-001) on RCT and the arterial vessel wall in FHA. Subjects received 20 infusions of CER-001 (8 mg/kg) during 6 months. Efficacy was assessed by measuring (apo) lipoproteins, plasma-mediated cellular cholesterol efflux, fecal sterol excretion (FSE), and carotid artery wall dimension by MRI and artery wall inflammation by F-18-fluorodeoxyglucose-positron emission tomography/computed tomography scans. We included seven FHA patients: HDL-cholesterol (HDL-c), 13.8 [1.8-29.1] mg/dl; apoA-I, 28.7 [7.9-59.1] mg/dl. Following nine infusions in 1 month, apoA-I and HDL-c increased directly after infusion by 27.0 and 16.1 mg/dl (P = 0.018). CER-001 induced a 44% relative increase (P = 0.018) in in vitro cellular cholesterol efflux with a trend toward increased FSE (P = 0.068). After nine infusions of CER-001, carotid mean vessel wall area decreased compared with baseline from 25.0 to 22.8 mm(2) (P = 0.043) and target-to-background ratio from 2.04 to 1.81 (P = 0.046). In FHA-subjects, CER-001 stimulates cholesterol mobilization and reduces artery wall dimension and inflammation,supporting further evaluation of CER-001 in FHA patients.
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