High-density lipoprotein remodeling by phospholipid nanoparticles improves cholesterol efflux capacity and protects from atherosclerosis.

Autor: Kudinov VA; Scientific Group of Phospholipid Drugs, Institute of Biomedical Chemistry, 119121 Moscow, Russia; Laboratory of Cell Biology and Developmental Pathology, FSBSI Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia. Electronic address: cd95@mail.ru., Torkhovskaya TI; Laboratory of Phospholipid Transport Systems and Nanomedicines, Institute of Biomedical Chemistry, 119121 Moscow, Russia. Electronic address: torti@mail.ru., Zakharova TS; Laboratory of Phospholipid Transport Systems and Nanomedicines, Institute of Biomedical Chemistry, 119121 Moscow, Russia. Electronic address: tz-post@list.ru., Morozevich GE; Laboratory of Protein Biosynthesis, Institute of Biomedical Chemistry, 119121 Moscow, Russia. Electronic address: galina.morozevich@ibmc.msk.ru., Artyushev RI; Scientific Group of Phospholipid Drugs, Institute of Biomedical Chemistry, 119121 Moscow, Russia. Electronic address: rifiraf21ibmx@gmail.com., Zubareva MY; Department of Atherosclerosis Problems, FSBI National Medical Research Center of Cardiology of the Ministry of Health of the Russian Federation, Moscow, Russia. Electronic address: mzubareva06@mail.ru., Markin SS; Clinical Research Department, Institute of Biomedical Chemistry, 119121 Moscow, Russia. Electronic address: comphos@mail.ru.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2021 Sep; Vol. 141, pp. 111900. Date of Electronic Publication: 2021 Jul 13.
DOI: 10.1016/j.biopha.2021.111900
Abstrakt: The efficiency of cholesterol efflux from cells promoted by high-density lipoproteins (HDLs) depends on HDL concentration and functional properties. The term "dysfunctional HDL" describes HDLs with impaired protective properties. Cholesterol efflux capacity (CEC) of HDL is reduced in patients with atherosclerosis, but the exact mechanisms underlying this impairment are not well characterized. Enriching HDLs with phospholipids (PLs) improves CEC. Herein, we assessed the potential of PL nanoparticles in improving HDL functionality. We lipidated HDL subfractions by incubating with PL nanoparticles containing soybean polyunsaturated phosphatidylcholine. Incubating blood plasma with PL nanoparticles resulted in the dose-dependent lipidation of all HDL subfractions. Changes in apolipoprotein A1 (apoA-1) and PL concentrations were the most prominent in the HDL 2 fraction. Concentrations of PL in the HDL 3 fraction and the fraction with a density > 1.21 g/mL increased by 30-50%, whereas apoA-1 levels decreased. We hypothesized that PL nanoparticles may cause HDL remodeling that can improve their functions. The CECs of lipidated HDLs were analyzed by incubating apolipoprotein B (apoB)-depleted plasma with 3 H-cholesterol-labeled THP-1 macrophages. The findings revealed a two-fold increase in cholesterol efflux compared with native apoB-depleted plasma. Moreover, intravenous administration of PL nanoparticles restored lipid profiles and effectively protected blood vessels from atherosclerosis progression in cholesterol-fed rabbits compared with that of fenofibrate and atorvastatin. PL nanoparticles also protected against atherosclerosis and decreased the atherogenic index. Altogether, these results indicate that PL nanoparticles can be used to correct the lipid composition and CEC of HDLs. DATA AVAILABILITY: Additional data can be provided upon reasonable request from the date of publication of this article within 5 years. The request should be sent to the author-correspondent at the address cd95@mail.ru.
(Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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