Abstract

Cholesteryl ester hydrolase (CEH) is a critical enzyme in cholesterol ester hydrolysis, influencing cholesterol metabolism and efflux. This study demonstrates that CEH overexpression promotes free cholesterol efflux from macrophages, thereby reducing the lipid burden in existing atherosclerotic plaques. To enable targeted delivery, galactose-functionalized polyamidoamine (PAMAM) dendrimeric nanoparticles were utilized as nanocarriers for hepatic delivery of the CEH expression vector. The therapeutic potential of CEH plasmid-loaded dendrimeric nanoparticles was evaluated in Ldlr-/- mice. Results showed a significant reduction in total lesion area (21%) and aortic arch lesion area (23%) compared to baseline. Lesion component analysis revealed marked decreases in total cholesterol (36%), free cholesterol (35%), and cholesterol esters (44%). Collectively, these results support CEH overexpression as an effective strategy to enhance cholesterol efflux and mitigate lipid accumulation in atherosclerotic plaques. Moreover, galactose-functionalized PAMAM dendrimeric nanoparticles demonstrate strong potential as a targeted hepatic gene delivery system for therapeutic intervention in atherosclerosis.

Department(s)

Chemical and Biochemical Engineering

Comments

National Institutes of Health, Grant R01HL140684

Keywords and Phrases

cholesterol efflux; cholesteryl ester hydrolase; galactose; gene delivery; hepatocyte targeting; PAMAM dendrimer

International Standard Serial Number (ISSN)

2575-9108

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2025 American Chemical Society, All rights reserved.

Publication Date

01 Jan 2025

Download

Full Text Link

Share

 
COinS