scholarly journals DNA methylation and gene expression integration in cardiovascular disease

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Guillermo Palou-Márquez ◽  
Isaac Subirana ◽  
Lara Nonell ◽  
Alba Fernández-Sanlés ◽  
Roberto Elosua
Keyword(s):  
Gene Expression ◽  
Cardiovascular Disease ◽  
Dna Methylation ◽  
Cardiovascular Diseases ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Risk Function ◽  
Predictive Biomarkers ◽  
Independent Study ◽  
Cell Type

Abstract Background The integration of different layers of omics information is an opportunity to tackle the complexity of cardiovascular diseases (CVD) and to identify new predictive biomarkers and potential therapeutic targets. Our aim was to integrate DNA methylation and gene expression data in an effort to identify biomarkers related to cardiovascular disease risk in a community-based population. We accessed data from the Framingham Offspring Study, a cohort study with data on DNA methylation (Infinium HumanMethylation450 BeadChip; Illumina) and gene expression (Human Exon 1.0 ST Array; Affymetrix). Using the MOFA2 R package, we integrated these data to identify biomarkers related to the risk of presenting a cardiovascular event. Results Four independent latent factors (9, 19, 21—only in women—and 27), driven by DNA methylation, were associated with cardiovascular disease independently of classical risk factors and cell-type counts. In a sensitivity analysis, we also identified factor 21 as associated with CVD in women. Factors 9, 21 and 27 were also associated with coronary heart disease risk. Moreover, in a replication effort in an independent study three of the genes included in factor 27 were also present in a factor identified to be associated with myocardial infarction (CDC42BPB, MAN2A2 and RPTOR). Factor 9 was related to age and cell-type proportions; factor 19 was related to age and B cells count; factor 21 pointed to human immunodeficiency virus infection-related pathways and inflammation; and factor 27 was related to lifestyle factors such as alcohol consumption, smoking and body mass index. Inclusion of factor 21 (only in women) improved the discriminative and reclassification capacity of the Framingham classical risk function and factor 27 improved its discrimination. Conclusions Unsupervised multi-omics data integration methods have the potential to provide insights into the pathogenesis of cardiovascular diseases. We identified four independent factors (one only in women) pointing to inflammation, endothelium homeostasis, visceral fat, cardiac remodeling and lifestyles as key players in the determination of cardiovascular risk. Moreover, two of these factors improved the predictive capacity of a classical risk function.

Differential DNA Methylation and Cardiometabolic Risk in African American Mother-Adolescent Dyads

2021 ◽  
pp. 109980042110390
Author(s):  
Amanda Elswick Gentry ◽  
Jo Robins ◽  
Mat Makowski ◽  
Wendy Kliewer
Keyword(s):  
Insulin Resistance ◽  
Cardiovascular Disease ◽  
Dna Methylation ◽  
African American ◽  
African Americans ◽  
Waist Circumference ◽  
Low Income ◽  
Cardiometabolic Risk ◽  
Disease Risk ◽  
Cardiovascular Disease Risk

Background: Cardiovascular disease disproportionately affects African Americans as the leading cause of morbidity and mortality. Among African Americans, compared to other racial groups, cardiovascular disease onset occurs at an earlier age due to a higher prevalence of cardiometabolic risk factors, particularly obesity, hypertension and type 2 diabetes. Emerging evidence suggests that heritable epigenetic processes are related to increased cardiovascular disease risk, but this is largely unexplored in adolescents or across generations. Materials and Methods: In a cross-sectional descriptive pilot study in low-income African American mother-adolescent dyads, we examined associations between DNA methylation and the cardiometabolic indicators of body mass index, waist circumference, and insulin resistance. Results: Four adjacent cytosine and guanine nucleotides (CpG) sites were significantly differentially methylated and associated with C-reactive protein (CRP), 62 with waist circumference, and none to insulin resistance in models for both mothers and adolescents. Conclusion: Further study of the relations among psychological and environmental stressors, indicators of cardiovascular disease, risk, and epigenetic factors will improve understanding of cardiovascular disease risk so that preventive measures can be instituted earlier and more effectively. To our knowledge this work is the first to examine DNA methylation and cardiometabolic risk outcomes in mother-adolescent dyads.

scholarly journals Cardiovascular disease risk factors induce mesenchymal features and senescence in cardiac endothelial cells

2020 ◽  
Author(s):  
Karthik Amudhala Hemanthakumar ◽  
Fang Shentong ◽  
Andrey Anisimov ◽  
Mikko I. Mäyränpää ◽  
Eero Mervaala ◽  
...  
Keyword(s):  
Gene Expression ◽  
Risk Factors ◽  
Cardiovascular Disease ◽  
Endothelial Cells ◽  
Exercise Training ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Pressure Overload ◽  
Cvd Risk Factors ◽  
Cvd Risk

AbstractAging, obesity, hypertension and physical inactivity are major risk factors for endothelial dysfunction and cardiovascular disease (CVD). We applied fluorescence-activated cell sorting (FACS), RNA sequencing and bioinformatic methods to investigate the common effects of CVD risk factors on cardiac endothelial cells (ECs). Aging, obesity and pressure overload all upregulated pathways related to TGF-β signaling and mesenchymal gene expression, inflammation, vascular permeability, oxidative stress, collagen synthesis and cellular senescence, whereas exercise training downregulated most of the same pathways. We identified collagen chaperone SerpinH1/HSP47 to be significantly increased by aging and obesity and repressed by exercise training. Mechanistic studies demonstrated that SERPINH1/HSP47 in human ECs changed cell morphology and increased mesenchymal gene expression, while its silencing inhibited collagen deposition. Our data demonstrate that CVD risk factors significantly remodel the transcriptomic landscape of cardiac ECs to acquire senescence and mesenchymal features. SERPINH1/HSP47 was identified as a potential therapeutic target in ECs.

scholarly journals Ultra-processed food intake and cardiovascular disease risk in the NutriNet-Santé prospective cohort

2019 ◽  
Vol 29 (Supplement_4) ◽  
Author(s):  
B Srour ◽  
L K Fezeu ◽  
E Kesse-Guyot ◽  
B Allès ◽  
E Chazelas ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Disease Risk ◽  
Saturated Fatty Acids ◽  
Cardiovascular Disease Risk ◽  
Food Additives ◽  
Cerebrovascular Diseases ◽  
Sensitivity Analyses ◽  
Processed Food ◽  
Increased Risk

Abstract Objective To assess the prospective associations between consumption of ultra-processed foods (UPF) and the risk of cardiovascular diseases. Methods 105159 participants aged at least 18 years (median age 41.5 years) from the French NutriNet-Santé cohort (2009-2018) were included. Dietary intakes were collected using repeated 24 hour dietary records, designed to register participants’ usual consumption for 3300 different food items, and categorized according to their degree of processing by the NOVA classification. Associations between UPF intake and risk of cardiovascular, coronary heart, and cerebrovascular diseases assessed by multivariable Cox proportional hazard models, adjusted for known risk factors. Results UPF intake was associated with higher cardiovascular disease risk (n = 1409 cases; HR for an absolute increment of 10 in the percentage of UPF = 1.12(1.05-1.20); P = 0.0008), coronary heart disease risk (n = 665 cases; HR = 1.13(1.02-1.24); P = 0.02), and cerebrovascular disease risk (n = 829 cases; HR = 1.11(1.01-1.22); P = 0.02). These results remained statistically significant after adjustment for several markers of the nutritional quality of the diet (saturated fatty acids, sodium and sugar intakes, dietary fiber or a Healthy pattern derived by principal component analysis) and after a large range of sensitivity analyses. Conclusions In this large observational prospective study, higher consumption of UPF was associated with higher risks of cardiovascular, coronary heart, and cerebrovascular diseases. These results need to be confirmed in other populations and settings, and causality remains to be established. Key messages The consumption of ultra-processed food is associated with an increased risk of cardiovascular diseases. As the French Public Helath agency recommends, their consumption should be limited. Nutritional composition, food additives, contact materials, or neoformed contaminants might play a role in these associations and further studies are needed to understand their relative contribution.

Cardiovascular Disease Risk Factors among Copper Industry Workers of the Sverdlovsk Region

2020 ◽  
pp. 33-37
Author(s):  
L.A. Konevskikh ◽  
T.T. Ladokhina ◽  
E.D. Konstantinova ◽  
S.G. Astakhova
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Occupational Risk ◽  
Cardiovascular Disease Risk Factors ◽  
Copper Industry ◽  
Cvd Risk ◽  
Occupational Risk Factors

Introduction. Cardiovascular diseases (CVD) are the leading cause of death in the working-age population including occupational deaths. Materials and methods. We conducted general clinical and biochemical studies among copper industry workers including a complete cholesterol test, blood lead and copper tests, volumetric sphygmography with determination of the cardio-ankle vascular index (CAVI), and ultrasound examination of the carotid arteries with intima-media thickness measurements (IMT). Results. We established that the main cardiovascular disease risk factors among our subjects were smoking (72.2%), different types of obesity (33.3%), total cholesterol levels higher than 4.9 mmol/L (57.9%), fasting hyperglycemia (73.9%), and hypertension stages 1 and 2 (40.7%). We also observed increased arterial stiffness by CAVI in 28.7% of the subjects that became more prevalent with the rise in the total CVD risk by SCORE (p=0.00105). Conclusions. We found correlations between CAVI and blood copper levels (r=0.33), years of exposure to occupational risk factors (r=0.187), and IMT (r=0.41). This finding enabled us to recommend the use of CAVI for identification and follow-up of workers at risk of cardiovascular diseases with a simultaneous decrease in exposures to occupational risk factors.

scholarly journals Cardiovascular disease risk factors and DNA methylation at theLINE-1repeat region in peripheral blood from Samoan Islanders

Epigenetics ◽  
2011 ◽  
Vol 6 (10) ◽  
pp. 1257-1264 ◽  
Author(s):  
Haley L. Cash ◽  
Stephen T. McGarvey ◽  
E. Andrés Houseman ◽  
Carmen J. Marsit ◽  
Nicola L. Hawley ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Dna Methylation ◽  
Peripheral Blood ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Cardiovascular Disease Risk Factors
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