化学
高密度脂蛋白
清道夫受体
脂蛋白
氧化应激
CD36
电源1
胆固醇
生物物理学
低密度脂蛋白
对氧磷酶
药理学
体内
炎症
生物化学
内科学
受体
医学
生物
基因
基因型
生物技术
作者
Yanyan Wang,Xinya Huang,Danni Yang,Jianhua He,Zhaoan Chen,Kexuan Li,Jianping Liu,Wenli Zhang
标识
DOI:10.1016/j.ejpb.2022.12.005
摘要
Numerous studies have demonstrated that dysfunctional high-density lipoprotein (HDL), especially oxidized HDL (OxHDL), could generate multifaceted in vivo proatherogenic effects that run counter to the antiatherogenic activities of HDL. It thereby reminded us that the in vitro reconstituted HDL (rHDL) might encountered with oxidation-induced dysfunction. Accordingly, a green-inspired method was employed to recycle non-split HDL from human plasma fraction IV. Then it was compared with rHDL formulated by an ethanol-injection method in terms of physicochemical properties and anti-dysfunctional activities. Results exhibited that rHDL oxidation extent exceeded that of non-split HDL evidenced by higher malondialdehy content, weaker inhibition on low-density lipoprotein (LDL) oxidation and more superoxide anion. The reserved paraoxonase-1 activity on non-split HDL could partially explain for above experimental results. In the targeted transport mechanism experiment, upon SR-BI receptor inhibition and/or CD36 receptor blockage, the almost unchanged non-split HDL uptake in lipid-laden macrophage indicated its negligible oxidation modification profile with regard to rHDL again. Furthermore, compared to rHDL, better macrophage biofunctions were observed for non-split HDL as illustrated by accelerated cholesterol efflux, inhibited oxidized LDL uptake and lessened cellular lipid accumulation. Along with decreased ROS secretion, obviously weakened oxidative stress damage was also detected under treatment with non-split HDL. More importantly, foam cells with non-split HDL-intervention inspired an enhanced inflammation repression and apoptosis inhibition effect. Collectively, the anti-dysfunctional activities of non-split HDL make it suitable as a potential nanocarrier platform for cardiovascular drug payload and delivery.
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