Study On The Interaction Between Low Density Lipoprotein And Anionic Ligands

The level of low density lipoprotein (LDL) in the human blood isclosely related to the atherosclerosis disease. Therefore, the removal ofLDL in blood is considered as the main route for the medical preventionand treatment of atherosclerosis. Among varies LDL removing methods,the removal of LDL in vitro has attracted wide attention for their efficiencyand conveniency. The development of new LDL adsorbents is still inurgent needs, and the selection of LDL adsorption ligands determines theLDL removal efficiency. So the studies on the interaction between ligandsand LDL have great significance in developing of LDL adsorbents. Herewe selected three kinds of anionic ligands (glutathione, dextran sulfate andheparin) that could adsorb LDL through electrostatic interaction, andinvestigated their interactions with LDL.Firstly, we studied the interaction between the three kinds of anionicligands and LDL by isothermal titration calorimetry (ITC), andthermodynamic parameters were obtained. The results showed that thethree kinds of ligands and LDL binding reactions were enthalpy-driven,and could occur spontaneously. The interaction constant values ofglutathione, dextran sulfate, heparin with LDL were3.42×106,2.08×106and1.31×106respectively, and the corresponding strength decreased in the following order: glutathione, dextran sulfate, and heparin. And spectralanalysis was carried out to further study the structural change of LDL afterligand combination. Fluorescence results showed the same trendconcerning the structural change of LDL after the interaction. Themaximum LDL fluorescence emission peak blue shifted6nm,5nm and2nm for glutathione, dextran sulfate and heparin respectively, whichindicated the increased hydrophobicity in the microenvironment of thefluorescent amino acid. Circular dichroism results also revealed the LDLsecondary structure (α-helix content) change after LDL interaction with thethree ligands, among which glutathione was the most effective one with anα-helix content decrease of3.4%followed by dextran sulfate and heparin.The spectral results indicated the glutathione had the strongest interactionwith LDL and the greatest impact on LDL structure change, which wereconsistent with the results of ITC.