Effects of LDL Apheresis System on the Expression of Genes Involved in Lipoprotein Metabolism and Inflammation in Homozygotes for Familial Hypercholesterolemia
Condition: Familial Hypercholesterolemia
MeSH terms: Hyperlipoproteinemia Type II; Hypercholesterolemia; Inflammation
Study type: Interventional

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.
    


Intervention name(s): Pre-lipid apheresis; Post-lipid apheresis
Intervention type(s): Other; Other
Intervention description(s): Blood samples will be taken just before the start of the lipid apheresis treatment.; Blood samples will be taken following the lipid apheresis treatment.
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment