Abstract
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.
Highlights
The atheroprotective effects of serum high-density lipoprotein (HDL) are largely ascribed to its anti-oxidative, anti-inflammatory, cholesterol efflux, and endothelial function, which partially rely on HDL-associated paraoxonase 1 (PON1) [1,2,3,4,5]
We found significantly higher PON1 content in HDL isolated from subjects with high compared to those with low Endothelial lipase (EL) serum levels (Figure 4A) and EL serum levels were significantly positively correlated with HDL PON1 content (Figure 4B)
We provide evidence that EL modulates HDL PON1 content and AE activity and that marked differences are observed in vitro and in vivo
Summary
The atheroprotective effects of serum high-density lipoprotein (HDL) are largely ascribed to its anti-oxidative, anti-inflammatory, cholesterol efflux, and endothelial function, which partially rely on HDL-associated paraoxonase 1 (PON1) [1,2,3,4,5]. Binding of the secreted PON1 to HDL involves an interaction of HDL with the hepatocyte surface, which is a process facilitated by scavenger receptor class B type I (SR-BI) [6,7]. The protein–protein and protein–lipid interactions between PON1 and HDL have been found to be crucial for the stability and enzymatic activity of HDL-associated PON1 [8,9,10]. In addition to its HDL-associated form, PON1 exists as a free enzyme, which can redistribute to cell membranes or can be taken up by cells [11,12]. The majority (95%) of secreted PON1 is associated with HDL, only a subset of circulating HDL particles (5–10%) contain PON1 [13,14,15,16]. It has been shown that the lipid and protein composition of PON1-containing HDL particles differ from HDL particles lacking PON1 [17]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
