Modulating lysophospholipids with Paraoxonase-1: Exploring its impact on inflammatory responses and immune reactions

Introduction: Paraoxonase-1 (PON1) is a crucial esterase in cardiovascular health, closely associated with HDL and known for its antioxidant and anti-inflammatory properties. Reduced PON1 activity has been linked to cardiovascular diseases. Lysophospholipids (LysoPLs), essential for cellular processes and immune responses, are implicated in the pathogenesis of cardiovascular diseases and are bound to lipoproteins, contributing to their diverse effects. Thus, we hypothesize that the relationship between PON1 and cardiovascular diseases may involve the modulation of LysoPLs by PON1. This study aims to investigate how PON1 potentially influences LysoPLs.

Methods: We quantified the levels of LysoPLs in HepG2 cells by using liquid chromatography-mass spectrometry, manipulating PON1 expression or knockdown.

Results: In cells overexpressing PON1, there was a significant increase in cellular levels of lysophosphatidylserine (LysoPS) and medium levels of LysoPS. Conversely, in cells with PON-1 knockdown, cellular levels of lysophosphatidylcholine (LysoPC) and medium levels of LysoPC showed a significant decrease.

Conclusions: PON1 is involved in modulating LysoPLs, which contribute to the antioxidant and anti-inflammatory properties of HDL, often attributed to PON1.