Analysis of SIRT1 Expression in Plasma and in an <i>In Vitro</i> Model of Preeclampsia

Viana-Mattioli, Sarah; Nunes, Priscila Rezeck; Cavalli, Ricardo Carvalho; Sandrim, Valéria C.

doi:10.1155/2020/4561083

Cited by 21 publications

(19 citation statements)

References 45 publications

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“…Notably, we found several important genes related to the pathophysiology of PE, such as matrix metallopeptidase 9 ( MMP-9 ), metastasis-associated lung adenocarcinoma transcript 1 ( MALAT1 ), transforming growth factor beta receptor 2 ( TGFBR2 ), and sirtuin-1 ( SIRT1 ). Noteworthy, SIRT1 was found to be downregulated by independent analyses in PE (Viana-Mattioli et al, 2020 ). Moreover, SIRT1 was shown to have a role in regulating endothelial function, arterial remodeling, and vascular aging (Man et al, 2019 ).…”

Section: Resultsmentioning

confidence: 98%

“…However, this previous study did not explore the target genes for the miRNA 204-5p nor the mechanisms of action of these target genes. Interestingly, we found that some of the target genes for the miRNA 204-5p were also found to be downregulated by independent analyses in PE, such as brain-derived neurotrophic factor ( BDNF ) (Perucci et al, 2017 ) and SIRT1 (Viana-Mattioli et al, 2020 ). For example, SIRT1 can deacetylate histones and lead to gene silencing, and it can also regulate the function of several target proteins by deacetylation (Gomes et al, 2016 ).…”

Section: Discussionmentioning

confidence: 98%

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Circulating MicroRNAs in the Second Trimester From Pregnant Women Who Subsequently Developed Preeclampsia: Potential Candidates as Predictive Biomarkers and Pathway Analysis for Target Genes of miR-204-5p

et al. 2021

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MicroRNAs (miRNAs) play an important role in the pathophysiology of preeclampsia (PE). However, the expression of circulating miRNAs was not analyzed in the second trimester of pregnancy, a period of major relevance to identify predictive biomarkers for PE. Therefore, we examined the expression profiles of 84 circulating miRNAs using a PCR array in plasma collected between 20 and 25 weeks of gestation from pregnant women, who subsequently developed PE and those who remained healthy during pregnancy, randomly selected from a prospective cohort. Overall, 23 miRNAs had a fold change > 2.0 and were considered to be upregulated in plasma from pregnant women who subsequently developed PE, even before the onset of clinical symptoms of PE. However, only miR-204-5p was statistically significant (P = 0.0082). Experimentally validated interactions for the target genes of miR-204-5p extracted from miRTarBase were used in the gene set functional enrichment analysis to identify Reactome pathways. The network connecting the 37 target genes for miR-204-5p revealed pathways of known pathophysiological relevance during the early development of PE and included key genes related to PE, such as BDNF, MMP-9, MALAT1, TGFBR2, and SIRT1. We further depicted downstream targets of SIRT1 that are related to the vascular endothelial function or implicated in the pathophysiology of PE, namely, FOXO1, NFκB, HIF-1α, NOS3, and PPAR-γ. Our novel findings provide for circulating miRNAs upregulated in the second trimester on plasma from pregnant women who subsequently developed PE that is potentially related to the early development of PE, which may guide further studies focused on the validation of potential predictive biomarkers in PE.

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Section: Resultsmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 98%

Circulating MicroRNAs in the Second Trimester From Pregnant Women Who Subsequently Developed Preeclampsia: Potential Candidates as Predictive Biomarkers and Pathway Analysis for Target Genes of miR-204-5p

et al. 2021

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“…Only a few studies on SIRT1 in HDPs pathogenesis are available. Reduced SIRT1 expression has been demonstrated in PE patients compared to PIH patients and healthy pregnant women, which may suggest a different pathogenetic background of PIH and PE [73]. Its decreased levels have been noticed in third-trimester placentas from patients with PE [74].…”

Section: Pathophysiology Of Preeclampsiamentioning

confidence: 97%

Prevention of Hypertensive Disorders of Pregnancy—Is There a Place for Metformin?

Poniedziałek‐Czajkowska

Mierzyński

Dłuski

et al. 2021

JCM

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The possibility of prophylaxis of hypertensive disorders of pregnancy (HDPs) such as preeclampsia (PE) and pregnancy-induced hypertension is of interest due to the unpredictable course of these diseases and the risks they carry for both mother and fetus. It has been proven that their development is associated with the presence of the placenta, and the processes that initiate it begin at the time of the abnormal invasion of the trophoblast in early pregnancy. The ideal HDP prophylaxis should alleviate the influence of risk factors and, at the same time, promote physiological trophoblast invasion and maintain the physiologic endothelium function without any harm to both mother and fetus. So far, aspirin is the only effective and recommended pharmacological agent for the prevention of HDPs in high-risk groups. Metformin is a hypoglycemic drug with a proven protective effect on the cardiovascular system. Respecting the anti-inflammatory properties of metformin and its favorable impact on the endothelium, it seems to be an interesting option for HDP prophylaxis. The results of previous studies on such use of metformin are ambiguous, although they indicate that in a certain group of pregnant women, it might be effective in preventing hypertensive complications. The aim of this study is to present the possibility of metformin in the prevention of hypertensive disorders of pregnancy with respect to its impact on the pathogenic elements of development

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“…As mentioned, our results show the upregulation of placental SIRT1 by citrulline. The expression of SIRT1, an nutrient sensor, is downregulated in preeclamptic women in comparison to healthy pregnant 97 . The SIRT1-peroxisome proliferator-activated receptor gamma (PPARγ) axis is proposed to be a key player in trophoblast differentiation and placental development 44 .…”

Section: Lipid Metabolismmentioning

confidence: 98%

L-citrulline ameliorates pathophysiology in a rat model of superimposed preeclampsia

Man

Zhou

Lam

et al. 2021

Preprint

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Preeclampsia, characterized by hypertension, proteinuria, and fetal growth restriction, is one of the leading causes of maternal and perinatal mortality. By far, there is no effective pharmacological therapy for preeclampsia. The present study was conducted to investigate the effects of L-citrulline supplementation in Dahl salt-sensitive rat, a model of superimposed preeclampsia. Parental DSSR were treated with L-citrulline (2.5 g/L in drinking water) from the day of mating to the end of lactation period. Blood pressure of the rats was monitored throughout pregnancy and markers of preeclampsia were assessed. Endothelial function of the pregnant DSSR was assessed by wire myograph. L-citrulline supplementation significantly reduced gestational hypertension, proteinuria, and levels of circulating soluble fms-like tyrosine kinase 1 in DSSR. L-citrulline improved maternal endothelial function by augmenting the production of nitric oxide in the aorta and improving endothelium-derived hyperpolarizing factor-mediated vasorelaxation in resistance arteries. L-citrulline supplementation improved placental insufficiency and fetal growth, which were associated with an enhancement of angiogenesis and reduction of fibrosis and senescence in the placentas. In addition, L-citrulline downregulated genes involved in the toll-like receptor 4 and nuclear factor-κB signaling pathway. In conclusion, this study shows that L-citrulline supplementation reduces gestational hypertension, improves placentation and fetal growth in a rat model of superimposed preeclampsia. L-citrulline supplementation may represent an effective and safe therapeutic strategy for preeclampsia that benefit both the mother and the fetus.

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Analysis of SIRT1 Expression in Plasma and in an In Vitro Model of Preeclampsia

Cited by 21 publications

References 45 publications

Circulating MicroRNAs in the Second Trimester From Pregnant Women Who Subsequently Developed Preeclampsia: Potential Candidates as Predictive Biomarkers and Pathway Analysis for Target Genes of miR-204-5p

Circulating MicroRNAs in the Second Trimester From Pregnant Women Who Subsequently Developed Preeclampsia: Potential Candidates as Predictive Biomarkers and Pathway Analysis for Target Genes of miR-204-5p

Prevention of Hypertensive Disorders of Pregnancy—Is There a Place for Metformin?

L-citrulline ameliorates pathophysiology in a rat model of superimposed preeclampsia

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