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Cholesterol removal by haemoperfusion of whole blood in vivo
Insights
New agarose beads effectively remove low-density lipoprotein cholesterol (LDL-C) from blood via hemoperfusion, offering a promising alternative to plasmapheresis for familial hypercholesterolemia treatment.
Area of Science:
- Biochemistry
- Medical Technology
- Cardiovascular Research
Background:
- Familial hypercholesterolemia (FH) involves genetic defects in cholesterol metabolism, leading to elevated LDL-C and atherosclerosis.
- Current treatments for FH often involve plasmapheresis, which is expensive and invasive.
- Efficient removal of LDL-C from plasma is crucial for managing FH and preventing cardiovascular events.
Purpose of the Study:
- To develop and evaluate a novel hemoperfusion (HP) system using modified agarose beads for selective LDL-C removal.
- To assess the efficacy and safety of this HP technique in an animal model of hypercholesterolemia.
- To explore a potential alternative to plasmapheresis for FH patients.
Main Methods:
- Agarose beads were prepared, crosslinked, and functionalized with heparin and/or ethanolamine.
- A hemoperfusion system utilizing a column packed with these active agarose beads was employed.
- The system was tested on hypercholesterolemic rabbits to evaluate LDL-C and HDL-C removal from whole blood.
Main Results:
- A single 2-hour HP treatment reduced plasma cholesterol levels by 30% in experimental rabbits.
- In vitro studies demonstrated high selectivity for LDL-C in human plasma.
- While effective for LDL-C, the rabbit model showed some removal of HDL-C, attributed to species-specific lipoprotein differences.
- No significant abnormalities were detected post-treatment, apart from a slight prolongation of prothrombin time (PT).
Conclusions:
- Modified agarose beads are effective for LDL-C removal via hemoperfusion in a rabbit model.
- This HP technique shows potential as a less invasive and more cost-effective alternative to plasmapheresis for managing hypercholesterolemia.
- Further research is needed to optimize selectivity and confirm efficacy in human trials, considering species differences in lipoprotein structure.
Abstract:
Familial hypercholesterolaemia is caused by genetic defects in the cellular metabolism of cholesterol (C) and is characterized by high levels of low-density lipoproteins (LDL) and premature atherosclerosis. The C is carried in the plasma mainly as an LDL-C complex, and removal of the latter from plasma is highly desirable. This task can be achieved by selective haemoperfusion (HP), thereby eliminating the need for plasmapheresis. Agarose beads (2 per cent agarose, 0.85 to 1.4 mm in diameter) were prepared, and crosslinked with epichlorohydrin. Heparin and/or ethanolamine were subsequently attached. The beads thus obtained were found to be suitable for the removal of LDL-C from the whole blood of hypercholesterolaemic rabbits, using a simple HP technique. A single two-hour HP treatment with a 40 ml column packed with active agarose beads resulted in a 30 per cent decrease in the C plasma level in the experimental animals. Our previous, in vitro, studies with the plasma of hypercholesterolaemic patients showed a high selectivity of the beads for LDL. Yet when used with hypercholesterolaemic rabbits, a relatively high amount of HDL was also removed from the blood. This can be attributed to a significant difference between the structure of human hypercholesterolaemic lipoproteins and that of rabbits. Upon treatment of blood using the active agarose beads, no abnormalities in plasma and blood composition were detected, except for some prolongation of PT. It is to be hoped that this new system will replace the presently used and highly expensive plasmapheresis.