Platelet-activating Factor–Acetyl Hydrolase is Associated with Dysregulated Expression of Nrf2-NQO1 Pathway in Metabolic Syndrome

Background: Vascular complications are commonly associated with metabolic syndrome (MetS) as a result of oxidative stress (OS) and inflammation.Platelet-activating factor-acetyl hydrolase (PAF-AH), a product of phospholipase A2 group VII (PLA2G7) gene, is a proinflammatory and proatherogenic protein.It is a marker for vascular inflammation and is associated with cardiovascular disease (CVD) risk.This study explores the relationship between PAF-AH, OS, and inflammation in MetS.Methods: One twenty-four participants were screened, out of which 45 patients with MetS and 35 controls were finally recruited.Markers of OS such as total antioxidant status (TAS), oxidized low-density lipoprotein (oxLDL), and malondialdehyde (MDA) and inflammatory markers like high-sensitivity C-reactive protein (hsCRP) and PAF-AH activity were analyzed in both groups.Messenger ribonucleic acid (mRNA) expression levels of PLA2G7, as well as cytoprotective genes nuclear erythroid-related factor 2 (Nrf2) and NADPH quinone oxidoreductase (NQO1), were assessed using quantitative polymerase chain reaction (qPCR).Results: MetS patients exhibited significantly elevated PAF-AH activity and oxLDL levels compared to controls.Although hsCRP and MDA levels were higher and TAS lower in MetS patients, these differences were not statistically significant.Higher mRNA expression of Nrf2 and PLA2G7 (2.46 and 3.03 folds, respectively), and reduced NQO1 expression (2.35 folds) was observed in MetS patients.Significant positive correlations were found between PLA2G7 expression and oxLDL levels, while negative correlations existed with TAS and Nrf2 expression. Conclusion:In MetS, risk factors for atherosclerosis (AS) are heightened, as reflected by increased expression and activity of the proatherogenic enzyme PAF-AH.A lower expression of genes involved in antioxidant defense may exacerbate OS in these patients.An imbalance in the expression of proinflammatory, proatherogenic, and antioxidant genes may underlie the increased risk of vascular complications in MetS.Clinical significance: Results of this study indicate that PAF-AH may be a potential therapeutic target in patients with MetS.