Effects of LDL Apheresis System on the Expression of Genes Involved in Lipoprotein Metabolism and Inflammation in Homozygotes for Familial Hypercholesterolemia

Summary

Familial hypercholesterolemia (FH) is an autosomal codominant single-gene disorder caused by mutations in the LDL receptor gene that disrupt the normal clearance of LDL particles from the plasma compartment. Heterozygous patients present a 2- to 3-fold raise in plasma LDL-cholesterol (C) concentrations, tendinous xanthomatosis and premature atherosclerotic coronary heart disease (CHD), usually occurring between the age of 35 and 55 years. Since the mid-1970s, LDL-C has been removed from the blood of patients using plasmapheresis, and this technique has been shown to improve the life expectancy of FH homozygotes. LDL apheresis selectively removes LDL particles but not immunoglobulins and other beneficial proteins, thereby overcoming a potential drawback of the traditional plasmapheresis method. LDL-C is effectively reduced by more than 60% immediately after LDL apheresis, although LDL levels rebound rapidly.

Dextran sulfate adsorption is a commonly apheresis technique used in familial hypercholesterolemia patients. In this apheresis plasma is separated from red blood cells and passed over columns of cellulose beads containing dextran sulfate which binds apolipoprotein B (apoB) by a highly selective electrostatic binding mechanism. Since LDL, very-low density lipoprotein (VLDL), and Lipoprotein (a) all contain apoB, dextran sulfate adsorption apheresis selectively reduces these lipoproteins while having little effect on the non-apoB containing HDL particles. In clinical practice, LDL apheresis reduces the rate of future cardiovascular events and has been postulated to have additional effects on potentially pro-atherogenic factors. Some proteins have been identified with adhesive characteristics to lipoproteins, rheological, immunological and inflammation relevant proteins16-19 that influence microcirculation as well as the inflammatory response. However, no studies have yet to investigate the impact of LDL apheresis on the expression of different genes involved in cardiovascular disease.

The main objective of the present research project is to investigate the impact of the LDL apheresis dextran sulfate adsorption system on the messenger ribonucleic acid (mRNA) expression of genes involved in cardiovascular disease using microarrays analysis in 9 FH homozygotes.

Conditions

• Familial Hypercholesterolemia

Interventions

OTHER

Pre-lipid apheresis

Blood samples will be taken just before the start of the lipid apheresis treatment.

OTHER

Post-lipid apheresis

Blood samples will be taken following the lipid apheresis treatment.

Sponsors & Collaborators

• Laval University

  lead OTHER

Principal Investigators

• Patrick Couture, MD,FRCP,PhD · Laval University

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

60 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2015-10-31

Primary Completion

2015-12-31

Completion

2016-02-29

Countries

• Canada

Study Locations