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Heparin degradation in the endothelial cells
T Barzu1, J L van Rijn, M Petitou
1INSERM U 150, Hôpital Lariboisière, LA 334 CNRS, Paris, France.
Thrombosis Research
|September 1, 1987
Summary
Human endothelial cells selectively internalize high molecular weight heparin. This internalized heparin undergoes depolymerization, likely via lysosomal enzymes, potentially affecting its anticoagulant activity.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Heparin is a widely used anticoagulant medication.
- Understanding heparin's interaction with endothelial cells is crucial for its therapeutic efficacy.
- The cellular mechanisms of heparin uptake and degradation are not fully elucidated.
Purpose of the Study:
- To investigate the molecular weight distribution of heparin fractions bound and internalized by human endothelial cells.
- To determine the cellular fate of internalized heparin.
- To explore the role of lysosomal enzymes in heparin degradation.
Main Methods:
- Gel permeation chromatography was used to analyze heparin fractions.
- (125I)-labeled heparin was employed to track uptake and internalization.
- The effect of chloroquine on heparin depolymerization was assessed.
Main Results:
- High molecular weight heparin chains were selectively bound and internalized by endothelial cells.
- Internalized heparin underwent depolymerization.
- Chloroquine inhibited heparin depolymerization, implicating lysosomal enzymes.
- Endothelial cell degradation of high molecular weight heparin may contribute to drug inactivation, particularly antifactor IIa activity.
Conclusions:
- Human endothelial cells exhibit selective uptake of high molecular weight heparin.
- Lysosomal enzymes are involved in the depolymerization of internalized heparin.
- Heparin degradation by endothelial cells could impact its anticoagulant efficacy.