Systematic evaluation of the effect of different apolipoprotein A-I mimetic peptides on the performance of synthetic high-density lipoproteins in vitro and in vivo.

Abstract

Synthetic high-density lipoproteins nanomedicine (sHDL) composed of apolipoprotein A-I (ApoA-I) mimetic peptides and lipids have shown very promising results for the treatment of various cardiovascular diseases. Numerous efforts have also been made to design different ApoA-I mimetic peptides to improve the potency of sHDL, especially the efficiency of reverse cholesterol transport. However, the way in which ApoA-I mimetic peptides affect the properties of sHDL, including stability, cholesterol efflux, cholesterol esterification, elimination in vivo, and the relationship of these properties, is still poorly understood. Revealing the effect of these factors on the potency of sHDL is important for the design of better ApoA-I mimetic peptides. In this study, three widely used ApoA-I mimetic peptides with different sequences, lengths, LCAT activation and lipid binding affinities were used for the preparation of sHDL and were evaluated in terms of physical/chemical properties, cholesterol efflux, cholesterol esterification, remodeling, and pharmacokinetics/pharmacodynamics. Our results showed that ApoA-I mimetic peptides with the highest cholesterol efflux and cholesterol esterification in vitro did not exhibit the highest cholesterol mobilization in vivo. Further analysis indicated that other factors, such as pharmacokinetics and remodeling of sHDL, need to be considered in order to predict the efficiency of cholesterol mobilization in vivo. Thus, our study highlights the importance of using the overall performance, rather than in vitro results alone, as the blueprint for the design and optimization of ApoA-I mimetic peptides.

• Authors: Wenmin Yuan, Kelsey Ernst, Rui Kuai, Emily E Morin, Minzhi Yu, Denis O Sviridov, Jie Tang, Ling Mei, Dan Li, Rose Ackermann, Alan T Remaley, Anna Schwendeman
• Journal: Nanomedicine : nanotechnology, biology, and medicine (Nanomedicine) Vol. 48 Pg. 102646 (02 2023) ISSN: 1549-9642 [Electronic] United States
• PMID: 36549559 (Publication Type: Journal Article)
• Copyright: Copyright © 2022. Published by Elsevier Inc.

Chemical References

• Lipoproteins, HDL
• Apolipoprotein A-I
• Peptides
• Cholesterol

Topics

• Lipoproteins, HDL (chemistry)
• Apolipoprotein A-I (pharmacology, chemistry)
• Peptides (pharmacology, chemistry)
• Cholesterol (chemistry)
• Biological Transport