Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Molecular Biology and Biochemistry, Medical University of Graz, Neue Stiftingtalstraße 6/6, 8010 Graz, Austria.
Otto Loewi Research Center, Division of Pharmacology, Medical University of Graz, Universitätsplatz 4, 8010 Graz, Austria.
Int J Mol Sci. 2021 Jan 13;22(2):719. doi: 10.3390/ijms22020719.
Endothelial lipase (EL) is a strong modulator of the high-density lipoprotein (HDL) structure, composition, and function. Here, we examined the impact of EL on HDL paraoxonase 1 (PON1) content and arylesterase (AE) activity in vitro and in vivo. The incubation of HDL with EL-overexpressing HepG2 cells decreased HDL size, PON1 content, and AE activity. The EL modification of HDL did not diminish the capacity of HDL to associate with PON1 when EL-modified HDL was incubated with PON1-overexpressing cells. The overexpression of EL in mice significantly decreased HDL serum levels but unexpectedly increased HDL PON1 content and HDL AE activity. Enzymatically inactive EL had no effect on the PON1 content of HDL in mice. In healthy subjects, EL serum levels were not significantly correlated with HDL levels. However, HDL PON1 content was positively associated with EL serum levels. The EL-induced changes in the HDL-lipid composition were not linked to the HDL PON1 content. We conclude that primarily, the interaction of enzymatically active EL with HDL, rather than EL-induced alterations in HDL size and composition, causes PON1 displacement from HDL in vitro. In vivo, the EL-mediated reduction of HDL serum levels and the consequently increased PON1-to-HDL ratio in serum increase HDL PON1 content and AE activity in mice. In humans, additional mechanisms appear to underlie the association of EL serum levels and HDL PON1 content.
内皮脂肪酶（EL）是高密度脂蛋白（HDL）结构、组成和功能的强有力调节剂。在这里，我们研究了 EL 对体外和体内 HDL 对氧磷酶 1（PON1）含量和芳基酯酶（AE）活性的影响。用过表达 EL 的 HepG2 细胞孵育 HDL 会降低 HDL 大小、PON1 含量和 AE 活性。当用过表达 PON1 的细胞孵育 EL 修饰的 HDL 时，EL 修饰的 HDL 并没有降低 HDL 与 PON1 结合的能力。EL 在小鼠中的过表达显著降低了 HDL 的血清水平，但出人意料的是增加了 HDL 的 PON1 含量和 HDL 的 AE 活性。无酶活性的 EL 对小鼠 HDL 中的 PON1 含量没有影响。在健康受试者中，EL 血清水平与 HDL 水平无显著相关性。然而，HDL 的 PON1 含量与 EL 血清水平呈正相关。EL 诱导的 HDL-脂质组成的变化与 HDL 的 PON1 含量无关。我们得出的结论是，主要是具有酶活性的 EL 与 HDL 的相互作用，而不是 EL 诱导的 HDL 大小和组成的改变，导致 PON1 在体外从 HDL 中置换。在体内，EL 介导的 HDL 血清水平降低和随之而来的血清中 PON1 与 HDL 比值的增加增加了小鼠 HDL 的 PON1 含量和 AE 活性。在人类中，EL 血清水平和 HDL PON1 含量之间的关联可能还有其他机制。
