Abstract
Chylomicron remnants have been suggested to be involved in the development of atherosclerosis. To investigate the mechanisms of chylomicron remnant-induced atherosclerosis, we prepared cholesterol (Chol)-containing emulsion particles as models for chylomicron remnants. Chol markedly increased the apolipoprotein E (apoE) binding maximum of emulsions without changing the binding affinity and thereby promoted emulsion uptake by J774 macrophages. Fluorescence measurements showed that Chol increased acyl chain order and head group hydration of the surface phospholipid (PL) layer of emulsions. The binding maximum of apoE was closely correlated with the hydration and the increase in the PL head group separation at the emulsion surface. From experiments using inhibitors for lipoprotein receptors, heparan sulfate proteoglycans and low density lipoprotein receptor-related protein were found to be the major contributors to the uptake of Chol-containing emulsions. Trypan blue dye exclusion revealed that the uptake of Chol-containing emulsions induced cytotoxicity to J774 macrophages. This study proposes a mechanism of atherosclerosis induced by chylomicron remnants.
Highlights
Chylomicron remnants have been suggested to be involved in the development of atherosclerosis
Effects of apolipoprotein E (apoE) on emulsion uptake by J774 macrophages We examined the contribution of apoE to the uptake of TO-PC and TO-PC/Chol emulsions by J774 macrophages
We tested whether cell surface heparan sulfate proteoglycan (HSPG) and lipoprotein receptorrelated protein (LRP) are involved in apoEmediated emulsion uptake by incubating J774 macrophages with emulsions in the presence of 100 g/ml heparin or 5 mg/ml lactoferrin (Fig. 2)
Summary
Chylomicron remnants have been suggested to be involved in the development of atherosclerosis. To investigate the mechanisms of chylomicron remnant-induced atherosclerosis, we used Chol-containing emulsion particles as models for chylomicron remnants and evaluated the effects of Chol enrichment on apoE-mediated emulsion uptake by J774 macrophages and the resulting cytotoxicity. Cell-surface heparan sulfate proteoglycans (HSPGs) and low density lipoprotein receptorrelated protein (LRP) play a critical role in apoE-enriched remnant uptake.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
