Different Proteomic Profiles Regarding Antihypertensive Therapy in Preeclampsia Pregnant.

Preeclampsia (PE) is a hypertensive pregnancy syndrome associated with target organ damage and increased cardiovascular risks, necessitating antihypertensive therapy. However, approximately 40% of patients are nonresponsive to treatment, which results in worse clinical outcomes. This study aimed to compare circulating proteomic profiles and identify differentially expressed proteins among 10 responsive (R-PE), 10 nonresponsive (NR-PE) patients, and 10 healthy pregnant controls (HP). We also explored correlations between these proteins and clinical data. Plasma protein relative quantification was performed using mass spectrometry, followed by bioinformatics analyses with the UniProt database, PatternLab for Proteomics 4.0, and MetaboAnalyst software (version 6.0). Considering a fold change of 1.5, four proteins were differentially expressed between NR-PE and R-PE: one upregulated (fibronectin) and three downregulated (pregnancy-specific beta-1-glycoprotein 1, complement C4B, and complement C4A). Between NR-PE and HP, six proteins were differentially expressed: two upregulated (clusterin and plasmin heavy chain A) and four downregulated (apolipoprotein L1, heparin cofactor II, complement C4B, and haptoglobin-related protein). Three proteins were differentially expressed between R-PE and HP: one downregulated (transthyretin) and two upregulated (apolipoprotein C1 and hemoglobin subunit beta). These findings suggest a complex interplay of these proteins involved in inflammatory, immune, and metabolic processes with antihypertensive therapy responsiveness and PE pathophysiology.

ARG2 single-nucleotide polymorphism rs3742879 affects plasma arginase 2 levels, nitric oxide formation and antihypertensive therapy response in preeclampsia.

Aim: This work examined whether ARG1 (rs2781659, rs2781667, rs2246012 and rs17599586) and ARG2 (rs3742879 and rs10483801) single-nucleotide polymorphisms (SNPs) are associated with antihypertensive therapy responsiveness in preeclampsia (PE) and their effects on arginase isoforms and nitrite concentrations in responsive and nonresponsive patients. Methods: SNP genotypes were determined by TaqMan assays. Plasma arginase levels were measured by ELISA and nitrite concentrations were measured using an ozone-based chemiluminescence assay. Results: The G allele for ARG2 rs3742879 (A>G) was less frequent in nonresponsive compared with responsive patients (15.5% vs 24.7%, respectively) and the G carriers of the nonresponsive subgroup had lower arginase 2 (9.2 ± 7.5 ng/ml vs 19.1 ± 17.3 ng/ml) and higher nitrite concentrations (110.2 ± 52.8 nM vs 78.5 ± 37.9 nM) than carriers of the AA genotype (all p < 0.05). Conclusion: ARG2 SNP rs3742879 is associated with diminished arginase 2 levels and increased nitric oxide formation in nonresponsive PE patients.

Effects of arginase genetic polymorphisms on nitric oxide formation in healthy pregnancy and in preeclampsia.

BACKGROUND AND AIMS: Preeclampsia is associated with reduced nitric oxide (NO) bioavailability. Arginase is related to NO synthesis, but relatively unexplored in preeclampsia. However, no previous study has examined whether variations in ARG1 and ARG2 genes affect NO bioavailability and the risk of preeclampsia. Here, we compared the alleles and genotypes of single nucleotide polymorphisms (SNPs) in ARG1 (rs2781659; rs2781667; rs2246012; rs17599586) and ARG2 (rs3742879; rs10483801) in healthy pregnant women and preeclampsia, and examined whether these SNPs affect plasma nitrite concentrations (a marker of NO formation) in these groups. METHODS: Genotypes for the ARG1 and ARG2 SNPs were determined by Taqman probe and plasma nitrite by an ozone-based chemiluminescence assay. RESULTS: Regarding ARG1 SNPs, the GG genotype and G allele frequencies for rs2781659, and the C allele frequencies for rs2246012 were higher in preeclampsia compared to healthy pregnant women. Moreover, the GG genotype for rs2781659 and the TT genotype for rs2781667 were associated with higher plasma nitrite in healthy pregnant. We found no association of ARG2 polymorphisms with preeclampsia or nitrite levels in the study groups. CONCLUSIONS: Our results suggest that SNPs of ARG1 increase the risk of preeclampsia and modulate plasma nitrite levels in healthy pregnant women.