Activity and distribution of plasma platelet‐activating factor acetylhydrolase in women with gestational diabetes mellitus and their neonates

Gao, Qian; He, Guolin; Zhang, Li; Bai, Huai; Liu, Xinghui; Fan, Ping

doi:10.1002/dmrr.2782

Cited by 11 publications

(14 citation statements)

References 30 publications

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“…HDL‐associated Lp‐PLA2 is highly acknowledged to be anti‐inflammatory, while LDL‐associated Lp‐PLA2 is proinflammatory; however, the underlying mechanisms have yet to be elucidated. Alterations in the distribution of Lp‐PLA2 between LDL and HDL were detected in patients with various diseases, including atherosclerosis, dyslipidemias, DM, and PCOS . However, the clinical consequences of these alterations were inadequately determined .…”

Section: Discussion and Prospectsmentioning

confidence: 99%

Lipoprotein‐associated phospholipase A2: The story continues

Huang

Wang

Shen

2019

Medicinal Research Reviews

123

140

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Inflammation is thought to play an important role in the pathogenesis of vascular diseases. Lipoprotein‐associated phospholipase A2 (Lp‐PLA2) mediates vascular inflammation through the regulation of lipid metabolism in blood, thus, it has been extensively investigated to identify its role in vascular inflammation‐related diseases, mainly atherosclerosis. Although darapladib, the most advanced Lp‐PLA2 inhibitor, failed to meet the primary endpoints of two large phase III trials in atherosclerosis patients cotreated with standard medical care, the research on Lp‐PLA2 has not been terminated. Novel pathogenic, epidemiologic, genetic, and crystallographic studies regarding Lp‐PLA2 have been reported recently, while novel inhibitors were identified through a fragment‐based lead discovery strategy. More strikingly, recent clinical and preclinical studies revealed that Lp‐PLA2 inhibition showed promising therapeutic effects in diabetic macular edema and Alzheimer's disease. In this review, we not only summarized the knowledge of Lp‐PLA2 established in the past decades but also emphasized new findings in recent years. We hope this review could be valuable for helping researchers acquire a much deeper insight into the nature of Lp‐PLA2, identify more potent and selective Lp‐PLA2 inhibitors, and discover the potential indications of Lp‐PLA2 inhibitors.

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Section: Discussion and Prospectsmentioning

confidence: 99%

Lipoprotein‐associated phospholipase A2: The story continues

Huang

Wang

Shen

2019

Medicinal Research Reviews

123

140

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“…Thus, controversy remains regarding whether plasma PAF-AH exerts a pro- or anti-inflammatory action. Given that H-PAF-AH, one of antioxidant enzymes of HDL, plays anti-inflammatory role [14, 19] and apoB-PAF-AH is associated with inflammation [13, 14, 24], it has recently been suggested that the relative distribution of the enzyme between apoB-containing lipoproteins and HDL determines its pro- or anti-inflammatory actions. Previous studies indicated that H-PAF-AH activity was decreased and the ratio of LDL-associated PAF-AH to H-PAF-AH activities and MDA levels were increased in women with PCOS, and the PAF-AH G994 → T gene mutation is a risk factor for PCOS [19, 20, 32].…”

Section: Discussionmentioning

confidence: 99%

“…Plasma platelet-activating factor (PAF) acetylhydrolase (PAF-AH), also known as lipoprotein-associated phospholipase A2 (Lp-PLA2), is mainly bound to apolipoprotein (apo) B-containing lipoproteins, particularly low-density lipoprotein (LDL), and a small portion is also associated with high-density lipoprotein (HDL) [13, 14]. The abnormalities of plasma PAF-AH activity, mass and/or distribution in lipoproteins are associated with atherosclerosis and inflammatory diseases [14–16].…”

Section: Introductionmentioning

confidence: 99%

“…The abnormalities of plasma PAF-AH activity, mass and/or distribution in lipoproteins are associated with atherosclerosis and inflammatory diseases [14–16]. Decreased HDL-associated PAF-AH (H-PAF-AH) activities, increased apoB-containing lipoprotein-associated PAF-AH (apoB-PAF-AH) activities and/or the ratio of apoB-PAF-AH to total or H-PAF-AH activity are associated with cardiovascular diseases [14], type 2 diabetes [17], gestational diabetes mellitus [13], pre-eclampsia [18], and polycystic ovary syndrome [19, 20] and might be markers for chronic inflammation in these patients.…”

Section: Introductionmentioning

confidence: 99%

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Effect of the R92H and A379V genotypes of platelet-activating factor acetylhydrolase on its enzyme activity, oxidative stress and metabolic profile in Chinese women with polycystic ovary syndrome

et al. 2017

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BackgroundThe G994T polymorphism in platelet-activating factor acetylhydrolase (PAF-AH) gene is associated with the risk of polycystic ovary syndrome (PCOS). The aim of this study was to investigate the relationship between R92H and A379V variants of the PAF-AH gene and the risk of PCOS and to evaluate the effects of the genotypes on PAF-AH activities and clinical, metabolic and oxidative stress indexes in Chinese women.MethodsA total of 862 patients with PCOS based on the Rotterdam consensus criteria and 750 control women from a population of Chinese Han nationality in the Chengdu area were studied from 2006–2015. PAF-AH genotypes were determined by PCR and restriction fragment length polymorphism analysis. Plasma PAF-AH, high-density lipoprotein (HDL)-associated PAF-AH (H-PAF-AH) and apolipoprotein (apo) B-containing lipoprotein-associated PAF-AH (apoB-PAF-AH) activities were measured using the trichloroacetic acid precipitation procedure with PAF C-16 as a substrate. Circulating markers of oxidative stress, including serum total oxidant status, total antioxidant capacity, oxidative stress index and malondialdehyde levels, and clinical and metabolic parameters were also analyzed.ResultsNo significant differences were observed in the frequencies of R92H and A379V genotypes and alleles of the PAF-AH gene between PCOS and control groups (P > 0.05). Compared with patients with the 92RR genotype, patients with H allele of R92H (RH + HH genotype) had significantly higher plasma PAF-AH and apoB-PAF-AH activities (P < 0.05) and tended to exhibit increased H-PAF-AH activity (P = 0.063) after adjusted for age and BMI. However, when serum LDL-C, HDL-C, TG and HOMA index were added as covariates, the comparisons no longer remained statistical significance (P > 0.05). There were no significant differences in clinical, hormonal, metabolic and circulating oxidative stress parameters and the frequencies of PAF-AH G449T genotype according to PAF-AH R92H or A379V genotyping in patients with PCOS and control women.ConclusionsThere were no significant associations between R92H and A379V variants of PAF-AH gene and risk of PCOS in Chinese women. The increased plasma PAF-AH and apoB-PAF-AH activities in patients with H allele of R92H are related to the R92 → H variation, changes in plasma lipoprotein levels, insulin resistance, aging, and gaining weight and thus may be involved in the pathogenesis of PCOS and the increased risks of future cardiovascular diseases.

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“…In pregnancies affected by GDM, maternal serum LpPLA 2 levels are elevated compared to healthy pregnant women 36 at time of delivery; no data on LpPLA 2 levels throughout gestation in GDM pregnancies exist. In GDM mothers, LpPLA 2 activity was associated with triglyceride levels, ApoB levels and LDL-C levels in multivariate regression analysis 36 .…”

Section: Introductionmentioning

confidence: 99%

Maternal Gestational Diabetes Mellitus increases placental and foetal lipoprotein-associated Phospholipase A2 which might exert protective functions against oxidative stress

Schliefsteiner

Hirschmugl

Kopp

et al. 2017

Sci Rep

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Increased Lipoprotein associated phospholipase A2 (LpPLA2) has been associated with inflammatory pathologies, including Type 2 Diabetes. Studies on LpPLA2 and Gestational Diabetes Mellitus (GDM) are rare, and have focused mostly on maternal outcome. In the present study, we investigated whether LpPLA2 activity on foetal lipoproteins is altered by maternal GDM and/or obesity (a major risk factor for GDM), thereby contributing to changes in lipoprotein functionality. We identified HDL as the major carrier of LpPLA2 activity in the foetus, which is in contrast to adults. We observed marked expression of LpPLA2 in placental macrophages (Hofbauer cells; HBCs) and found that LpPLA2 activity in these cells was increased by insulin, leptin, and pro-inflammatory cytokines. These regulators were also increased in plasma of children born from GDM pregnancies. Our results suggest that insulin, leptin, and pro-inflammatory cytokines are positive regulators of LpPLA2 activity in the foeto-placental unit. Of particular interest, functional assays using a specific LpPLA2 inhibitor suggest that high-density lipoprotein (HDL)-associated LpPLA2 exerts anti-oxidative, athero-protective functions on placental endothelium and foetus. Our results therefore raise the possibility that foetal HDL-associated LpPLA2 might act as an anti-inflammatory enzyme improving vascular barrier function.

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Activity and distribution of plasma platelet‐activating factor acetylhydrolase in women with gestational diabetes mellitus and their neonates

Abstract: The mothers with GDM presented with a state of chronic inflammation, and these mothers and their neonates also exhibited unfavourable metabolic profiles in terms of glucose and lipids. Copyright © 2016 John Wiley & Sons, Ltd.

Cited by 11 publications

References 30 publications

Lipoprotein‐associated phospholipase A2: The story continues

Lipoprotein‐associated phospholipase A2: The story continues

Effect of the R92H and A379V genotypes of platelet-activating factor acetylhydrolase on its enzyme activity, oxidative stress and metabolic profile in Chinese women with polycystic ovary syndrome

Maternal Gestational Diabetes Mellitus increases placental and foetal lipoprotein-associated Phospholipase A2 which might exert protective functions against oxidative stress

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