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Start Over Topic epigenetics Publication Type Electronic Resources
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1. Molecular and Cellular Mechanisms of Preeclampsia.

Author

Huppertz, Berthold and Huppertz, Berthold

Subjects
Biology, life sciences, Research & information: general, AGE, Atg7, Body mass index (BMI), CCL2, CmklR1, DNA methylation, FGR, Gal 10, Gal 13, Gal 14, Gal 16, H19, HOX genes, IL-11, IL-6, IUGR, LPS, PE, Placental protein 13, RAGE, RARRES, TNF-α, adipocyte, angiogenesis, animal models of human disease, asymmetric dimethylarginine, autonomic nervous system, autophagy, baroreflex sensitivity, biomarkers, blunted cardiac response, cardiovascular adaptations, cardiovascular dysfunction, cardiovascular risk, cardiovascular/cerebrovascular diseases, cerebral cytokines, chemerin, children, decidua, eNOS, eNOS-knockout, echocardiography, endothelial dysfunction, epigenetics, erythropoiesis, exosomes, hematopoietic stem/progenitor cells, highly active anti-retroviral therapy, histone post translational modifications, homocysteine, human immunodeficiency virus, hydroxychloroquine, hypertensive disorders of pregnancy, immune response, inflammasomes, inflammation, intra-uterine growth restriction, invasion, low dose aspirin, low protein diet, lymphangiogenesis, lysosomes, macrophage, maternal cardiovascular system, metabolism 3, miR-210, miRNAs, micro-bleeds, microRNA expression, microglia, monocyte, n/a, nitric oxide, non coding RNAs, obstetrics 4, p62/SQSTM1, phosphocreatine 2, placenta, placental bioenergetics 1, placental insufficiency, placentation, polymorphism, preeclampsia, pregnancy, pregnancy complications, pregnancy outcome, prehypertension/hypertension, primary prevention, protein aggregation, risk prediction, sEng, sFlt-1, screening, speckle tracking echocardiography, trophoblast, umbilical cord blood, uterine artery, uterine glands, uterine milk, vagal withdrawal
Abstract

Summary: This Special Issue on the "Molecular and Cellular Mechanisms of Preeclampsia" belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics" of the International Journal of Molecular Sciences. It was a very successful Special Issue as it contains 20 published papers, including one editorial, nine original research papers, and ten reviews on the topic. The original publications cover a wide spectrum of topics, including alterations and involvement of specific factors during preeclampsia, new non-invasive technologies to identify changes, new treatment options, animal models, gender aspects, and effects of the pregnancy pathology later in life. The review publications again cover a wide spectrum of topics, including factors and pathways involved in preeclampsia, effects on the maternal vascular and immune systems, effects on the placenta and the trophoblast, epigenetic changes, new preventive strategies, and new views on the current hypotheses on preeclampsia. Taken together, this Special Issue gives a fantastic overview on a broad spectrum of topics, all of which are important to identify the real etiology of preeclampsia and to finally develop real treatment options.

2. Epigenetic signatures of chronic inflammation and their relation to brain structure and function across the lifecourse

Author

Conole, Eleanor Lucy Shepherd, Cox, Simon, Marioni, Riccardo, Miron, Veronica, Whalley, Heather, and Bastin, Mark

Subjects
DNA methylation, Inflammation, neuroimaging, Cognitive Ageing, Epigenetics
Abstract

Chronic inflammation is considered a key contributor to individual differences in brain ageing. However, there remains conflicting evidence about the exact brain structural and functional consequences of chronic inflammation. Part of this ambiguity comes from the lack of robust biomarkers used to characterise chronic inflammation, with most studies conflating acute vs chronic inflammation and relying on single time point sampling of highly phasic inflammatory markers from blood. Recent research indicates the potential of epigenetics to circumvent this issue, in particular the use of DNA methylation (DNAm) to provide a biological archive of inflammatory burden. DNAm is an epigenetic mechanism that regulates gene expression and acts as an interface by which lifestyle and environment can influence phenotype; alterations in DNAm are increasingly investigated as proxies for certain exposures, traits, and conditions. This thesis explores chronic inflammation and its relation to brain health using a multi-omic approach, examining associations of proteomic and DNA methylation signatures of inflammation with brain measures from structural and diffusion MRI and cognitive ability at different stages of the lifecourse. Following introductory chapters presenting overviews of epigenetics, inflammation and neuroimaging and cognitive metrics, the empirical work of this thesis examines these interrelationships in three population cohorts covering the human lifespan: from infancy in Theirworld Edinburgh Birth cohort (TEBC; age < 1 year), to mid to late adulthood in Stratifying Longitudinal Resilience & Depression Longitudinally cohort (STRADL; age ~ 60 years, range 28 - 81 years), to older-age in the Lothian Birth Cohort 1936 (LBC1936; age ~ 73 years). First, neuroimaging and cognitive associations of chronic inflammation in older age are examined. In 521 individuals from the LBC 1936 cohort, associations between a DNA methylation predictor of C-Reactive Protein (DNAm CRP) and brain structure and cognition are shown to be consistently stronger (6.4-fold greater on average) than those with traditional serum CRP measures: with higher DNAm CRP levels significantly associated with global and regional brain atrophy (β range |0.200| to |0.150|), differences in white matter microstructure and white matter hyperintensity burden (β range |0.099| to |0.162|), and poorer global and domain- specific cognitive functioning (β range |0.095| to |0.158|). This paper also demonstrates that the association between inflammation and cognitive ability is partially mediated by brain structure (up to 29.7%), dependent on lifestyle and health factors. The second empirical chapter replicates this association of an epigenetic inflammatory signature with brain and postnatal health outcomes in early life. In a neonatal cohort of 258 infants, the relationship between DNAm CRP with perinatal health and neuroimaging outcomes is investigated. The results support the theory that DNAm may be leveraged to capture a more cumulative impact of inflammatory burden, with DNAm CRP being higher in preterms compared to term infants and higher DNAm CRP levels associating with perinatal inflammatory-related morbidities (such as late onset sepsis and histologic chorioamnionitis) both individually and in aggregate (OR range |2.00 | to |4.71|). The main finding - that elevated DNAm CRP associates with poorer measures of white matter, both globally and regionally (β range |0.206| to |0.371|) - is considered in the context of how early birth associates with an increase in immune-related risks, which coincide with windows of neurodevelopmental plasticity, highlighting the vulnerability of developing white matter to inflammatory insults. Finally, the brain health associations of signatures of inflammation in midlife are considered. In 709 participants from the STRADL cohort, DNAm signatures for CRP alongside a range of other inflammatory-immune mediators are constructed and compared against protein levels in relation to neuroimaging and cognitive metrics. 73 unique DNAm signatures associated with numerous aspects of global brain structure and cognitive ability (β range |0.097| to |0.200|), alongside regional atrophy across the brain's cortex (β range |0.087| to |0.260|) and focal vulnerability of specific white matter tract microstructure (β range |0.103| to |0.185|). Many of these DNAm-brain associations were larger than the analogous proteome-brain associations, broadly independent of immune-cell proportions, clinical risk factors, and had previously been linked to various age-related diseases, reinforcing the central role that inflammation plays in health trajectories. The results of this chapter suggest that associations with chronic inflammation and brain structure are apparent in mid to late adulthood and may precipitate and underlie changes in cognitive functioning seen in older-age. This PhD characterises the global and regional associations of chronic inflammation on brain structure at different stages of life, elucidating new perspectives on how these mechanisms may be contributing to individual differences in cognitive ability. I highlight the potential of the developing field of epigenetics to offer a solution to the traditional limitations of assessing inflammatory burden in human cohorts, and how this may be used to gain a better understanding of how inflammation relates to aberrant neurodevelopment and cognitive decline. These findings provide new insights about the extent of inflammation's impact on brain health, as well as highlighting the utility of DNAm for risk prediction and stratification in relation to brain health outcomes.

Published
2023
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3. Emerging Role of Lipids in Metabolism and Disease.

Author

Pallottini, Valentina, Pallottini, Valentina, and Segatto, Marco

Subjects
Medicine, ATM, BDNF, BET proteins, Cholesterol, DNA damage response, Fatty acids, G-protein coupled receptors, HMGCR, JQ1, LDLr, Lipid mediators, Lipids, Lipophagy, SOD, SREBP, Sphingolipids, TFEB, TMEM97, acid sphingomyelinase, adiponectin, adipose tissue, angiogenesis, atherosclerosis, autotaxin, brain, breast cancer, breast reconstruction, cardiovascular disease, cell proliferation, cell signaling, cholesterol, chronic inflammation, diabetes mellitus, double strand breaks, eicosanoids, endothelial cell, epicardial fat thickness, epigenetics, epinephrine, fatty acid, female, frontal cortex, gender, glyceride, haptoglobin, high-cholesterol diet, high-density lipoprotein, high-sensitivity c-reactive protein, hippocampus, hyperglycemia, ionizing radiation, ischemia, ischemic stroke, leptin, lipid, lipid droplets, lipid mediators, lipid metabolism, lipid metabolism diseases, lipid storage diseases, lipocalin, lipolysis, lipophagy, lipoproteins, liver, lysocardiolipin acyltransferase, lysophosphatidic acid, mTORC1, metabolic reprogramming, metabolic stress, metabolism, mutations, neutral sphingomyelinase, nuclear sphingolipids, oral drug absorption, oxidative stress, oxidized phospholipids, p53, pathology, phosphatidylinositol 4,5-bisphosphate, phospholipase A2 (PLA2), phospholipase C, phospholipase D, phospholipid, polyunsaturated fatty acids, prodrug, prostaglandins, pulmonary fibrosis, radiation, sphingolipids, sphingomyelin metabolism, sphingosine kinase 1, sphingosine-1-phosphate, steroid, synaptic proteins, visceral fat thickness
Abstract

Summary: Even though initially considered as a passive means for storing energy, lipids are now regarded as multifaceted molecules with crucial structural and functional activities. For instance, some of them play essential roles as key components of cell membranes whereas others act as signaling molecules in the regulation of cell homeostasis. In recent years, lipid research has attracted increasing interest because of the involvement of this class of compounds in human health. Indeed, a plethora of pathological conditions are characterized by alterations in lipid metabolism, such as cardiovascular diseases and brain disorders. This Special Issue is a collection of papers from different experts in lipid research, with the aim of providing new insights into the physiopathological involvement of lipids and their impact on human health. This collection also demonstrates the usefulness of interdisciplinary approaches in the development of novel methods to study and manipulate lipid metabolism, which may represent an attractive target for designing effective therapeutic strategies to counteract numerous pathologies.