Interaction of arterial proteoglycans with low density lipoproteins(LDLs):From theory to promising therapeutic approaches

Although atherosclerosis is a multifactorial process,proteoglycans mediated lipoprotein(LDL)retention at the subendothelial space is a necessary and sufficient event in provoking lesion initiation.Proteoglycans(PGs)are usually composed of one core protein backbone with one or more glycosaminoglycan chains(GAGs)covalently linked,mainly include perlecan,biglycan,versican,and decorin.The interaction between LDL and proteoglycans is apparently mediated by the basic amino acids in apoB-100,the moiety of LDL,electrostatic interacting with the negatively charged GAGs(sulfate or carbohydrate groups)of proteoglycans or though some bridge molecules like sphingomyelinase(SMase)or lipoprotein lipase(LpL).In the later section,we collate the promising therapeutic approaches that have been proposed up to now,targeting LDL-PGs interaction.It should be concluded that previous studies on interaction between LDL and PGs mainly focused on perlecan,biglycan,decorin,and versican that all located in the extracellular matrix(ECM),future studies should pay more attention to the endothelial surface glycocalyx and its interaction with LDLs,seeking promising therapeutic targets more specifically.

Hydroxyapatite reinforced inorganic-organic hybrid nanocomposite as high-performance adsorbents for bilirubin removal in vitro and in pig models

Highly efficient removal of bilirubin from whole blood directly by hemoperfusion for liver failure therapy remains a challenge in the clinical field due to the low adsorption capacity,poor mechanical strength and low biocompatibility of adsorbents.In this work,a new class of nanocomposite adsorbents was constructed through an inorganic-organic co-crosslinked nanocomposite network between vinyltriethoxysilane(VTES)-functionalized hydroxyapatite nanoparticles(V-Hap)and non-ionic styrene-divinylbenzene(PS-DVB)resins(PS-DVB/V-Hap)using suspension polymerization.Notably,our adsorbent demonstrated substantially improved mechanical performance compared to the pure polymer,with the hardness and modulus increasing by nearly 3 and 2.5 times,respectively.Moreover,due to the development of a mesoporous structure,the prepared PS-DVB/V-Hap3 exhibited an ideal adsorption capacity of 40.27 mg·g^(-1).More importantly,the obtained adsorbent beads showed outstanding blood compatibility and biocompatibility.Furthermore,in vivo extracorporeal hemoperfusion verified the efficacy and biosafety of the adsorbent for directly removing bilirubin from whole blood in pig models,and this material could potentially prevent liver damage and improve clinical outcomes.Taken together,the results suggest that PS-DVB/V-Hap3 beads can be used in commercial adsorption columns to threat hyperbilirubinemia patients through hemoperfusion,thus replacing the existing techniques where plasma separation is initially required.