High-density lipoproteins (HDL) play an important role in the reverse cholesterol transport (RCT) pathway, contributing to the efflux of excess cellular cholesterol. However, the classic hypothesis that raising HDL-cholesterol (HDL-C) concentrations reduces cardiovascular disease (CVD) risk has been challenged by recent intervention studies. Nowadays, improving cholesterol efflux capacity of HDL particles is considered to be a better target for the prevention of CVD. We will first briefly summarize assays that have been developed in order to quantify HDL-mediated cholesterol efflux from macrophages. However, the main purpose of this review is to discuss factors and ABC-transporters that are associated with HDL-mediated cholesterol efflux, such as HDL particle characteristics (i.e. HDL size and composition), subjects' characteristics (i.e. gender, BMI and age), HDL-C raising drugs, lifestyle, genetic background, as well as acute and low-grade systemic inflammation. Results suggested that factors associated with small HDL particles efficiently promote cholesterol efflux via the ABCA1 transporter. This appears to contradict findings from epidemiological studies suggesting that in particular large HDL₂ particles are related to a reduced CVD risk. It is therefore essential not only to understand targets to increase cholesterol efflux capacity, but also to prove causality between cholesterol efflux capacity and the prevention of CVD risk.

高密度脂蛋白（HDL）在胆固醇逆向转运（RCT）途径中起着重要作用，导致过多的细胞胆固醇外流。然而，最近的干预研究挑战了提高HDL-胆固醇（HDL-C）浓度可降低心血管疾病（CVD）风险的经典假设。如今，提高HDL颗粒的胆固醇外排能力被认为是预防CVD的更好目标。我们将首先简要概述已开发的测定方法，以定量从巨噬细胞中HDL介导的胆固醇流出。但是，本综述的主要目的是讨论与HDL介导的胆固醇外流有关的因素和ABC转运蛋白，例如HDL颗粒特征（即HDL大小和组成），受试者特征（即 性别，BMI和年龄），提高HDL-C的药物，生活方式，遗传背景以及急性和低度全身性炎症。结果表明，与小HDL颗粒相关的因素可通过ABCA1转运蛋白有效促进胆固醇外流。这似乎与流行病学研究的发现相矛盾，这表明特别是大型HDL_2个颗粒与降低CVD风险有关。因此，不仅要了解增加胆固醇外排量的目标，而且要证明胆固醇外排量与预防CVD风险之间存在因果关系，这一点至关重要。