MiR-133a-3p/Sirt1 epigenetic programming mediates hypercholesterolemia susceptibility in female offspring induced by prenatal dexamethasone exposure

Li, Xufeng; Hu, Wen; Li, Li; Chen, Ze; Jiang, Tao; Zhang, Dingmei; Liu, Kexin; Wang, Hui

doi:10.1016/j.bcp.2022.115306

Cited by 15 publications

(22 citation statements)

References 57 publications

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“…42 However, in the female offspring, liver cholesterol synthesis was continuously enhanced, with characteristic hypercholesterolemic changes in the early stage (postnatal week 12). 32 These results suggest that dexamethasone exposure during pregnancy can increase the susceptibility to hypercholesterolemia in adult rats of different genders. Exposure to simvastatin during pregnancy disrupts blood cholesterol levels in male fetal rats, which is related to low androgen levels.…”

Section: Hypercholesterolemia Has An Intrauterine Developmental Originmentioning

confidence: 84%

“…25 Female human newborns of mothers treated with dexamethasone during pregnancy displayed increased cord blood TCH levels. 32 Similarly, the nonobese offspring of parents with diabetes presented an elevated blood TCH/HDL-C ratio before puberty. 31 It is suggested that an adverse environment during the intrauterine period can lead to an increase in blood cholesterol levels in the early postnatal period.…”

Section: Hypercholesterolemia Has An Intrauterine Developmental Originmentioning

confidence: 99%

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Intrauterine developmental origin, programming mechanism, and prevention strategy of fetal‐originated hypercholesterolemia

Liu,

Chen,

et al. 2023

Obesity Reviews

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SummaryThere is increasing evidence that hypercholesterolemia has an intrauterine developmental origin. However, the pathogenesis of fetal‐originated is still lacking in a theoretical system, which makes its clinical early prevention and treatment difficult. It has been found that an adverse environment during pregnancy (e.g., xenobiotic exposure) may lead to changes in fetal blood cholesterol levels through changing maternal cholesterol metabolic function and/or placental cholesterol transport function and may also directly affect the liver cholesterol metabolic function of the offspring in utero and continue after birth. Adverse environmental conditions during pregnancy may also raise maternal glucocorticoid levels and promote the placental glucocorticoid barrier opening, leading to fetal overexposure to maternal glucocorticoids. Intrauterine high‐glucocorticoid exposure can alter the liver cholesterol metabolism of offspring, resulting in an increased susceptibility to hypercholesterolemia after birth. Abnormal epigenetic modifications are involved in the intrauterine programming mechanism of fetal‐originated hypercholesterolemia. Some interventions targeted at pregnant mothers or offspring in early life have been proposed to effectively prevent and treat the development of fetal‐originated hypercholesterolemia. In this paper, the recent research progress on fetal‐originated hypercholesterolemia was reviewed, with emphasis on intrauterine maternal glucocorticoid programming mechanisms, in order to provide a theoretical basis for its early clinical warning, prevention, and treatment.

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Section: Hypercholesterolemia Has An Intrauterine Developmental Originmentioning

confidence: 84%

Section: Hypercholesterolemia Has An Intrauterine Developmental Originmentioning

confidence: 99%

Intrauterine developmental origin, programming mechanism, and prevention strategy of fetal‐originated hypercholesterolemia

Liu,

Chen,

et al. 2023

Obesity Reviews

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“…STAT1 [493], JAK2 [494], NOTCH2 [495], PDGFC (platelet derived growth factor C) [143], RASA1 [262], TLR6 [496], NOD2 [482], JMJD1C [483], CAVIN1 [485], POU2F1 [497], RPS5 [498] and LGALS3 [499] are involved in the regulation of cardiac fibrosis. TLR4 [500], ABCA1 [501], CCR2 [502], LDLR (low density lipoprotein receptor) [503], SIRT1 [504] and NOD2 [505] might crucially contribute to the development of hypercholesterolemia. ABCA1 [506], TLR5 [507], PTGS2 [508], TGFA (transforming growth factor alpha) [509], PDK4 [510], JAK2 [511], TLR2 [512], NEK7 [513], CCR1 [514], BACH1 [515], NCOA4 [195], LATS2 [516], PELI1 [517], EGR1 [518], CYBB (cytochrome b-245 beta chain) [519], MEFV (MEFV innate immuity regulator, pyrin) [520], CLEC4E [521], GCLC (glutamate-cysteine ligase catalytic subunit) [522], KLF3 [523], TP53INP1 [524], ITGB1 [525], IRF9 [526], PHLPP1 [527], NOD2 [528], ACSL4 [529], FGL2 [530], PF4 [531], VEGFB (vascular endothelial growth factor B) [532], CCR7 [533], IGFBP4 [534], TRPM4 [535], BAG1 [536], LGALS3 [537] and ATAD3A [538] could induce ischemic heart disease.…”

Section: Discussionmentioning

confidence: 99%

“…SIRT1 [481], STAT1 [473] and IRF9 [479] were a diagnostic biomarkers of cardiac hypertrophy and could be used as therapeutic targets. Studies had shown that SIRT1 [504] and IFITM3 [49] were associated with hypercholesterolemia. Studies have found that STAT1 [493] is altered expression in cardiac fibrosis, which can be used as a prognostic marker for cardiac fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Identification of novel prognostic targets in coronary artery disease and related complications using bioinformatics and next generation sequencing data analysis

Vastrad¹,

Vastrad²

2023

Preprint

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Coronary artery disease (CAD) is the most common cardiovascular disorder and the leading cause of heart related deaths in world. Increasing molecular targets have been discovered for CAD and CAD - related complications prognosis and therapy. However, there is still an urgent need to identify novel biomarkers. Therefore, we evaluated biomarkers that might help the diagnosis and treatment of CAD and CAD related complications. We searched next generation sequencing (NGS) dataset (GSE202625) and identified differentially expressed genes (DEGs) by comparing CAD and normal control samples using DESeq2. Gene ontology (GO) and pathway enrichment analyses of the DEGs were performed using the g:Profiler online database. The protein protein interaction (PPI) network was plotted with IMEx interactome and visualized using Cytoscape. Module analysis of the PPI network was done using PEWCC1. MiRNA hub gene regulatory network and TF hub gene regulatory network analysis was performed to identify the hub genes, miRNAs and TFs. Receiver operating characteristic (ROC) curve analysis was used to predict the diagnostic effectiveness of the hub genes. A total of 118 DEGs (479 up regulated genes and 479 down regulated genes) were detected. The GO enrichment analysis indicated that the DEGs most significantly enriched in cellular response to stimulus and biosynthetic process. The REACTOME pathway enrichment analysis revealed that the DEGs were most significantly enriched in immune system and eukaryotic translation elongation. PPI network, modules, miRNA hub gene regulatory network and TF hub gene regulatory network analysis demonstrated that EGR1, SIRT1, STAT1, LRRK2, HIF1A, CSNK2B, RPS3, RPS2, RPS4X and HDAC11 were the hub genes. On the whole, the findings of this study enhance our understanding of the potential molecular mechanisms of CAD and CAD-related complications, and provide potential targets for further research.

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“…In rat experiments, antenatal DEX exposure activated inositol 1,4,5-trisphosphate (IP3) receptor and L-type Ca 2+ channels, especially IP3R1 and Cav1.2, which increased phenylephrine-mediated vascular contractility in offspring by epigenetic regulation of altering promoter histone modification ( Xu et al, 2022 ). Li et al (2022a ) revealed that miRNA-mediated epigenetic regulation participated in the programming of hypercholesterolemia in female offspring after intrauterine DEX exposure. The experiment found that the application of DEX promoted glucocorticoid receptor nuclear translocation and miR-133a-3p, with the inhibition of Sirt1(101).…”

Section: Molecular Mechanisms Involved In Prenatal Drug Exposure-asso...mentioning

confidence: 99%

The molecular mechanisms in prenatal drug exposure-induced fetal programmed adult cardiovascular disease

Zhou

Hua

et al. 2023

Front. Pharmacol.

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The “developmental origins of health and disease” (DOHaD) hypothesis posits that early-life environmental exposures have a lasting impact on individual’s health and permanently shape growth, structure, and metabolism. This reprogramming, which results from fetal stress, is believed to contribute to the development of adulthood cardiovascular diseases such as hypertension, coronary artery disease, heart failure, and increased susceptibility to ischemic injuries. Recent studies have shown that prenatal exposure to drugs, such as glucocorticoids, antibiotics, antidepressants, antiepileptics, and other toxins, increases the risk of adult-onset cardiovascular diseases. In addition, observational and animal experimental studies have demonstrated the association between prenatal drug exposure and the programming of cardiovascular disease in the offspring. The molecular mechanisms underlying these effects are still being explored but are thought to involve metabolism dysregulation. This review summarizes the current evidence on the relationship between prenatal drug exposure and the risk of adult cardiovascular disorders. Additionally, we present the latest insights into the molecular mechanisms that lead to programmed cardiovascular phenotypes after prenatal drug exposure.

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MiR-133a-3p/Sirt1 epigenetic programming mediates hypercholesterolemia susceptibility in female offspring induced by prenatal dexamethasone exposure

Cited by 15 publications

References 57 publications

Intrauterine developmental origin, programming mechanism, and prevention strategy of fetal‐originated hypercholesterolemia

Intrauterine developmental origin, programming mechanism, and prevention strategy of fetal‐originated hypercholesterolemia

Identification of novel prognostic targets in coronary artery disease and related complications using bioinformatics and next generation sequencing data analysis

The molecular mechanisms in prenatal drug exposure-induced fetal programmed adult cardiovascular disease

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