Cardiology Medical News about HDL biosynthesis defect

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Identification of a novel human cellular HDL biosynthesis defect
European Heart Journal, 06/30/09

Rashid S et al. – Results indicate for the first time in humans that phospholipid and cholesterol efflux are 2 separate and distinct processes in cellular high-density lipoprotein (HDL) biosynthesis and that normal cellular phospholipid efflux is necessary for formation of larger {alpha}-HDL particles. Defective ABCA1 protein regulation results in a defect in phospholipid efflux, treatable with physiological oxysterols, a current therapeutic target that may serve to raise HDL levels in severe HDL deficiencies, pending further study.

Methods

Study of the cellular basis of a novel HDL-deficiency phenotype
Screen of 54 subjects of French Canadian ancestry with severe HDL deficiency
Exclusion of pts with mutations in genes currently associated with low HDL (ABCA1, LCAT, APOA-I, and SMPD1)

Results

Cellular phospholipid efflux impaired in HDL biosynthesis process but cholesterol efflux normal in 2 pts
On 2-dimensional gel electrophoresis analysis, the 2 impaired phospholipid efflux pts primarily defective in larger {alpha}-HDL subpopulations
In fibroblasts from affected subjects, oxysterol stimulation resulted in increased ABCA1 protein expression and normalized defective phospholipid efflux defect

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Congenital disorders of glycosylation: An update on defects affecting the biosynthesis of dolichol-linked oligosaccharides
Human Mutation, 11/02/09 Relevance Score: 65%%

Congenital disorders of glycosylation: An update on defects affecting the biosynthesis of dolichol-linked oligosaccharides
Human Mutation, 10/30/09 Relevance Score: 65%%

A New Mechanism for Bile Acid Diarrhea: Defective Feedback Inhibition of Bile Acid Biosynthesis
Clinical Gastroenterology and Hepatology, 11/04/09 Relevance Score: 64%%

Abnormal function of high-density lipoprotein is associated with poor disease control and an altered protein cargo in rheumatoid arthritis
Arthritis & Rheumatism, 10/01/09 Relevance Score: 48%%

Raising HDL cholesterol in women
International Journal of Women's Health, 11/18/09 Relevance Score: 47%%