Abstract
To explore the anti-atherosclerotic effects of recombinant high-density lipoproteins (rHDL) of apolipoprotein AI wild-type (apoA-Iwt), apolipoprotein AI Milano (apoA-IM), apolipoprotein AI (N74C) (apoA-I (N74C) )and apolipoprotein AV (apoA-V). We constructed rHDL liposomes (rHDLs), which included apoA-Iwt, apoA-IM, and apoA-I (N74C), followed by the synthesis of rHDLs, with the indicated ratios of apoA-Iwt, apoA-IM, apoA-I (N74C) and apoA-V. We investigated the anti-atherosclerotic effects by experiments including the DMPC clearance assay and experiments that assessed the in vitro antioxidation against low-density lipoprotein, the cellular uptake of oxidized low-density lipoprotein (oxLDL) and the in vitro intracellular lipid accumulation. Electron microscopy results revealed that as more apoA-V was present in rHDLs, the particle size of rHDLs was larger. The DMPC clearance assay subsequently showed that rHDL protein mixtures could promote DMPC turbidity clearance when more apoA-V was included in the reaction mixtures, with apoAV-rHDL showing the strongest turbidity clearance ability (P<0.05 vs AI-rHDL). In vitro antioxidation against low-density lipoprotein assays indicated that rHDLs containing apoA-V had increasing oxidation resistance against low-density lipoprotein (LDL) with higher apoA-V contents. Finally, cellular uptake of oxLDL and intracellular lipids suggested an apparent oxidation resistance to LDL oxidation in vitro and a reduced intracellular lipid accumulation in THP-1-derived macrophages, with AIM-rHDL demonstrating the greatest ability to decrease intracellular lipid accumulation. Different proportions of apolipoprotein A-I cysteine mutants and apolipoprotein A-V of rHDL changed the lipid binding capacity, particle size, and antioxidant capacity. These changes may show a beneficial effect of rHDL on atherosclerosis.
Highlights
An increasing number of studies have focussed on atherosclerosis (AS), which is caused by the accumulation of plaque in the lining of arteries, resulting in cardiovascular disease, cerebral infarction, and peripheral vascular disease
The original mass ratio of DPPC: apolipoproteins was 3.35:1 and the recombinant high-density lipoproteins (rHDL) were identified by electron microscopy
The results from the DMPC turbidity clearance assay showed that in each group, larger K values were obtained when more apoA-V was added to the rHDL mixtures, with the apoA-V group demonstrating the highest K value (P
Summary
An increasing number of studies have focussed on atherosclerosis (AS), which is caused by the accumulation of plaque in the lining of arteries, resulting in cardiovascular disease, cerebral infarction, and peripheral vascular disease. Coronary Heart Disease (CAD) is the main cause of death worldwide, leading to approximately 30% of the annual global mortality. [1] Some studies have shown that a high HDL level can clearly decrease the risk of AS. HDL proteins mainly act on reverse cholesterol transport (RCT) and have many other helpful biological functions, including antioxidative, anti-inflammatory, vasodilatory, antithrombotic, and cytoprotective effects [2,3,4,5]. ApoA-Iwt constitutes approximately 70% of HDL proteins [6], which plays an important role in RCT, lowering the level of triglycerides. ApoA-Iwt is an apolipoprotein with multiple biological functions and the major function is to stimulate RCT, which plays a key role
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