Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Streicher, J; Valent, P; Schmidt, H; Sengölge, G; Wagner, O; Strobl, W; Hörl, WH; Derfler, K.
Up-regulation of LDL-receptor expression by LDL-immunoapheresis in patients with familial hypercholesterolemia.
J Investig Med. 1999; 47(8):378-387
Web of Science
PubMed
- Co-Autor*innen der Med Uni Graz
- Schmidt Helena
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- Abstract:
- BACKGROUND: Familial hypercholesterolemia (FH) is characterized by an autosomal dominantly inherited deficiency of LDL-receptor expression on the cell surface, leading to excess plasma LDL-cholesterol and severe premature atherosclerosis. In patients with heterozygous FH, a major therapeutic objective of conventional drug therapy is to stimulate maximally the residual cellular capacity to produce LDL-receptors via inhibition of endogenous cholesterol synthesis. In contrast, LDL-immunoapheresis aims at reducing the plasma LDL-cholesterol level by extracorporeal elimination of LDL particles. The present study investigates whether LDL-immunoapheresis applied in addition to conventional drug therapy is able to further stimulate residual LDL-receptor expression capacity in patients with heterozygous FH via the withdrawal of external cholesterol supply, thereby exerting a second accessory lipid lowering effect. METHODS: LDL-receptor expression--calculated by transforming mean fluorescence intensities into numbers of antibody binding sites per cell (S/C)--was determined flow-cytometrically on peripheral blood monocytes before and after LDL-apheresis. For a comparison with the maximum obtainable receptor expression capacity, in vitro stimulation experiments under completely LDL deficient conditions were performed. RESULTS: Prior to LDL-apheresis, LDL-receptor density was comparable in patients (N = 7; 2014 +/- 359 S/C) and controls (N = 10; 1782 +/- 252 S/C). Under in vitro conditions LDL-receptor expression of controls exceeded that of patients with FH by 1.6 times. Immediately after apheresis, LDL-receptor expression significantly increased to almost the same level as obtained by in vitro stimulation (3640 +/- 423 S/C and 3632 +/- 572 S/C). The LDL-receptor expression in FH subsequent to LDL-apheresis exhibited two patterns of kinetics [Type 1: maximal receptor stimulation (288 +/- 70%; P < 0.07) already during apheresis; Type 2: highest receptor density 24 hours after treatment (149 +/- 11%; P < 0.01)]. CONCLUSIONS: These results demonstrate that despite drug therapy, LDL-apheresis significantly stimulates the residual LDL-receptor expression in FH via the reduction of available extracellular cholesterol resulting in delayed reappearance of hypercholesterolemia in between treatments.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Binding Sites, Antibody -
- Blood Component Removal - methods
- Cells, Cultured - methods
- Cholesterol, LDL - blood
- Female - blood
- Flow Cytometry - blood
- Humans - blood
- Hyperlipoproteinemia Type II - metabolism
- Immunosorbent Techniques - metabolism
- Leukocytes, Mononuclear - immunology
- Male - immunology
- Middle Aged - immunology
- Receptors, LDL - metabolism
- Up-Regulation - metabolism
- Find related publications in this database (Keywords)
- LDL-Cholesterol
- LDL-Apheresis
- Flow Cytometry
- LDL-Receptor