Polymers of lys (plys) and arg (parg) were found to be efficient Inhibitors of the formation of complexes between low density lipoprotein (LDL) and human chondroltln-6-sulfate-rlch proteoglycans. Displacement curves Indicate that efficiency was dependent on molecular weight Inclusion of alanlne In the polymer up to a 1:1 molar ratio (plys.ala) has a moderate effect on displacing capacity. Poly-L-lys (plys) and poly-L-arg (parg) exhibited similar displacing ability. Inclusion of tryptophan In plys and parg diminished their effect, whereas Inclusion of serine In plys.ssr (3M) Improved It Plys (18.3 kD) stimulates LDL binding to human fibroblasts. This may be due to the association of polylyslne to LDL, leading to an Increase In Its positive charge. These more positively charged LDL may have an Increased association with the negatively charged region of the apollpoproteln B/E receptor. Perfuslon experiments on rabbit aortic segments were used to measure the Influx of12SI-LDL Into the IrrtJma and to study the effect of basic polypeptides. Plys In a 10:1 molar ratio decreased the LDL uptake by approximately 25% when added to the system together with the LDL or In experiments In which the tissue segments were pre-perfused with plys, and LDL was added after elimination of the plys. The results suggest that polycationlc polypeptides, due to their strong affinity for sulfated proteoglycans, Interfere with the interactions of LDL with components of the arterial extracellular matrix.
Arteriosclerosis – Wolters Kluwer Health
Published: Sep 1, 1990