对氧磷酶 1 与高密度脂蛋白、抗氧化剂和巨噬细胞的相互作用调节动脉粥样硬化形成——高密度脂蛋白磷脂的保护作用。

Paraoxonase 1 interactions with HDL, antioxidants and macrophages regulate atherogenesis - a protective role for HDL phospholipids.

机构信息

The Lipid Research Laboratory, Technion Faculty of Medicine, the Rappaport Family Institute for Research in the Medical Sciences and Rambam Medical Center, Haifa, Israel.

出版信息

Adv Exp Med Biol. 2010;660:153-66. doi: 10.1007/978-1-60761-350-3_14.

DOI:10.1007/978-1-60761-350-3_14

PMID:20221878

Abstract

Macrophage cholesterol accumulation and foam cell formation is the hallmark of early atherogenesis. In addition to macrophages, at least three more major players regulate atherosclerosis development; paraoxonase 1 (PON1), antioxidants, and HDL. PON1 is an HDL-associated lactonase which posses antioxidant and anti-atherogenic properties. PON1 protects against macrophage-mediated LDL oxidation, and increases HDL binding to macrophages which, in turn, stimulates HDL's ability to promote cholesterol efflux. These two major anti-atherogenic properties of HDL (and of PON1) require, at least in part, macrophage binding sites for HDL-associated PON1. Indeed, PON1, as well as HDL-associated PON1, specifically binds to macrophages, leading to anti-atherogenic effects. Macrophage PON1 binding sites may thus be a target for future cardioprotection therapy. Studying the interactions among PON1, antioxidants, and macrophages can thus assist in achieving appropriate treatment and prevention of atherosclerosis.

摘要

巨噬细胞胆固醇积累和泡沫细胞形成是动脉粥样硬化早期发生的标志。除了巨噬细胞，至少还有另外三个主要参与者调节动脉粥样硬化的发展；对氧磷酶 1（PON1）、抗氧化剂和高密度脂蛋白（HDL）。PON1 是一种与 HDL 相关的内酯酶，具有抗氧化和抗动脉粥样硬化的特性。PON1 可防止巨噬细胞介导的 LDL 氧化，并增加 HDL 与巨噬细胞的结合，进而刺激 HDL 促进胆固醇流出的能力。HDL（和 PON1）的这两个主要抗动脉粥样硬化特性至少部分需要 HDL 相关 PON1 的巨噬细胞结合位点。事实上，PON1 以及与 HDL 相关的 PON1 特异性地与巨噬细胞结合，从而产生抗动脉粥样硬化作用。因此，巨噬细胞 PON1 结合位点可能是未来心脏保护治疗的靶点。研究 PON1、抗氧化剂和巨噬细胞之间的相互作用可以帮助实现对动脉粥样硬化的适当治疗和预防。