Institute of Cardiovascular and Medical Science, College of Medical Veterinary and Life Science, University of Glasgow, Wolfson Link Building, University Avenue, Glasgow G12 8QQ, U.K.
Occupational and Environmental Medicine Centre, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.
Clin Sci (Lond). 2020 Nov 27;134(22):2977-2986. doi: 10.1042/CS20200892.
High-density lipoprotein (HDL) is a circulating complex of lipids and proteins known primarily for its role in reverse cholesterol transport and consequent protection from atheroma. In spite of this, therapies aimed at increasing HDL concentration do not reduce the risk of cardiovascular disease (CVD), and as such focus has shifted towards other HDL functions protective of vascular health - including vasodilatory, anti-inflammatory, antioxidant and anti-thrombotic actions. It has been demonstrated that in disease states such as CVD and conditions of insulin resistance such as Type 2 diabetes mellitus (T2DM), HDL function is impaired owing to changes in the abundance and function of HDL-associated lipids and proteins, resulting in reduced vascular protection. However, the gold standard density ultracentrifugation technique used in the isolation of HDL also co-isolates extracellular vesicles (EVs). EVs are ubiquitous cell-derived particles with lipid bilayers that carry a number of lipids, proteins and DNA/RNA/miRNAs involved in cell-to-cell communication. EVs transfer their bioactive load through interaction with cell surface receptors, membrane fusion and endocytic pathways, and have been implicated in both cardiovascular and metabolic diseases - both as protective and pathogenic mediators. Given that studies using density ultracentrifugation to isolate HDL also co-isolate EVs, biological effects attributed to HDL may be confounded by EVs. We hypothesise that some of HDL's vascular protective functions in cardiovascular and metabolic disease may be mediated by EVs. Elucidating the contribution of EVs to HDL functions will provide better understanding of vascular protection and function in conditions of insulin resistance and potentially provide novel therapeutic targets for such diseases.
高密度脂蛋白（HDL）是一种循环脂质和蛋白质复合物，主要因其在胆固醇逆转运中的作用以及由此产生的抗动脉粥样硬化作用而闻名。尽管如此，旨在增加 HDL 浓度的治疗方法并不能降低心血管疾病（CVD）的风险，因此，研究重点已转向其他对血管健康具有保护作用的 HDL 功能，包括血管舒张、抗炎、抗氧化和抗血栓作用。已经证明，在 CVD 等疾病状态和 2 型糖尿病（T2DM）等胰岛素抵抗情况下，由于与 HDL 相关的脂质和蛋白质的丰度和功能发生变化，HDL 功能受损，导致血管保护作用降低。然而，用于分离 HDL 的黄金标准密度超速离心技术也会共分离细胞外囊泡（EVs）。EVs 是普遍存在的细胞衍生颗粒，具有脂质双层，携带许多参与细胞间通讯的脂质、蛋白质和 DNA/RNA/miRNAs。EVs 通过与细胞表面受体的相互作用、膜融合和内吞途径来传递其生物活性负载，并与心血管和代谢疾病有关，既是保护因子也是致病因子。鉴于使用密度超速离心分离 HDL 的研究也会共分离 EVs，归因于 HDL 的生物学效应可能会因 EVs 而变得复杂。我们假设，HDL 在心血管和代谢疾病中的一些血管保护功能可能是由 EVs 介导的。阐明 EVs 对 HDL 功能的贡献将有助于更好地理解胰岛素抵抗情况下的血管保护和功能，并为这些疾病提供新的治疗靶点。
