Epigenetics in Cardiovascular Disease

Front-Matter_2021_Epigenetics-in-Cardiovascular-Disease
Front Matter
Copyright_2021_Epigenetics-in-Cardiovascular-Disease
Copyright
Contributors_2021_Epigenetics-in-Cardiovascular-Disease
Contributors
Preface_2021_Epigenetics-in-Cardiovascular-Disease
Preface
The burden of cardiovascular disease
Central dogma of molecular biology
Epigenetic mechanisms
Epigenetic mechanisms as biomarkers and treatment targets in CVD
The EU-CardioRNA COST Action: networking to advance science
Presentation of the book and chapters
Acknowledgments
References
Chapter-1---The-ever-growing-burden-of-cardi_2021_Epigenetics-in-Cardiovascu
The ever-growing burden of cardiovascular disease
Introduction
Financial load of cardiovascular disease
Risk factors and health(y) behaviors
Risk factors
Hypertension
Cholesterol
Diabetes mellitus
Obesity
Health behaviors
Smoking
Alcohol
Physical inactivity
Vegetable and fruit consumption
Cardiovascular morbidity
Incidence and prevalence of cardiovascular disease
Incidence and Prevalence of ischemic heart disease
Incidence and prevalence of stroke
Incidence and prevalence of peripheral vascular disease
Incidence and prevalence of heart failure: growing problem
Incidence and prevalence of atrial fibrillation
Disability-adjusted life years due to cardiovascular disease
Mortality in cardiovascular disease
Premature cardiovascular mortality
References
Chapter-2---Epigenetics-concepts--An-ov_2021_Epigenetics-in-Cardiovascular-D
Epigenetics concepts: An overview
From general concepts to molecular mechanisms
DNA methylation
Posttranslational modifications of histones
Histone acetylation
Histone methylation
Histone phosphorylation
Chromatin remodeling and transcription
Noncoding RNAs
RNA modifications
Cardiovascular epigenetics
Epigenetics and cardiac development
Postnatal growth and maturation of the heart
Adult heart disease
Conclusions
Acknowledgments-Sources of funding
References
Chapter-3---From-classical-signaling-pathway_2021_Epigenetics-in-Cardiovascu
From classical signaling pathways to the nucleus
Introduction
Ca2+-dependent changes in gene expression
Ca2+-/calmodulin-dependent kinase II
Protein kinase C
CAMTA2
Ca2+-dependent regulation of alternative splicing
cAMP-dependent epigenetic regulation
Protein kinase A (PKA)
PKA and lipid droplet-associated signaling
Nuclear retention of class IIa HDACs
A-kinase-anchoring proteins (AKAPs) and cAMP compartmentalization signaling
Antagonistic roles of Ca2+ and cAMP signaling
Translational perspective
Future directions
Source of funding
References
Chapter-4---DNA-methylation-in-heart-fa_2021_Epigenetics-in-Cardiovascular-D
DNA methylation in heart failure
DNA methylation in the heart
Preface
Mechanisms of DNA methylation and demethylation
Mechanisms that regulate DNA methylation and demethylation
The DNA methylation landscape
DNA methylation in the healthy heart
DNA methylation in cardiac disease
Studies in humans hearts
DNA methylation in animal models of heart failure
Targeting DNA methylation for therapy
DNA methylation signature as biomarkers for heart failure
Future outlook
References
Chapter-5---Histone-modifications-in-cardiovascul_2021_Epigenetics-in-Cardio
Histone modifications in cardiovascular disease initiation and progression
Introduction
DNA and chromatin structure
Histone variants
Histone variants in the heart
Histone turnover in the heart
Histone modifications: The fundamentals
Histone modifiers and readers
Histone acetyltransferases
Histone deacetylases (HDACs)
Class I HDACs
Class IIa and Class IIb HDACs
Class III HDACs: Sirtuins
Class IV HDAC: HDAC11
Histone-independent roles of HDACs
Histone methyltransferases (HMTs)
Euchromatic lysine methyltransferases 1 and 2 (EHMT1/2)
Suppressor of Variegation 3-9 Homolog (SUV39H1/2)
SET and MYND domain-containing proteins (SMYDs)
Disruptor of telomeric silencing 1-like (DOT1L)
Histone arginine methyltransferases (PRMTs)
Histone lysine demethylases (KDMs)
Histone modifications in cardiomyocyte differentiation, development, and proliferation
Cardiomyocyte remodeling in development and disease
Pharmaceutical targeting of epigenetic modifiers and modifications in CVD
HDAC inhibitors (HDACi)
Histone-independent roles of HDACi
DNA methyltransferase inhibitors (DNMTi)
Bromodomain and extraterminal domain inhibition (BETi)
Histone profiling and personalized medicine
Conclusion and future perspectives
References
Chapter-6---RNA-modifications-in-cardiovascular-dise_2021_Epigenetics-in-Car
RNA modifications in cardiovascular disease-An experimental and computational perspective
Introduction
m6A mRNA methylation
m6A methylases and m6A demethylases
m6A readers
m6A in cardiovascular disease
m6A in heart failure
m6A and regulation of cell growth
m6A and response to ischemia
Mechanisms and outlook
Modification mapping approaches
Antibody-based methods
MeRIP-seq/LAIC-seq
miCLIP
Antibody-free methods
Reverse transcription signatures
Enzymatic methylation-sensitive RNA digest
Nanopore direct RNA sequencing
Acknowledgments
References
Chapter-7---Regulatory-RNAs-in-cardiovascu_2021_Epigenetics-in-Cardiovascula
Regulatory RNAs in cardiovascular disease
Introduction
Noncoding RNAs
MicroRNAs
Long noncoding RNAs
Circular RNAs
Regulatory RNAs in myocardial infarction
MiRNAs and myocardial infarction
LncRNA in myocardial infarction
CircRNAs in myocardial infarction
Noncoding RNAs in cardiac remodeling and heart failure
MiRNAs in cardiac remodeling and heart failure
LncRNAs in cardiac remodeling and heart failure
CircRNAs in cardiac remodeling and heart failure
Regulatory RNAs in arrhythmias
miRNAs in arrhythmias
LncRNAs in arrhythmias
Translational perspective and conclusions
Funding
References
Chapter-8---Regulation-of-splicing-in-cardio_2021_Epigenetics-in-Cardiovascu
Regulation of splicing in cardiovascular disease
RNA splicing, constitutive splicing, and alternative splicing
Splicing and noncoding RNAs
Regulation of RNA splicing
Gene architecture
RNA transcription and elongation speed
Variation within splice site consensus sequences
Cis-regulatory sequences and transacting factors
The epitranscriptome
Chromatin epigenetic marks
RNA secondary structures
Interactions with other RNA molecules
Splicing factors in the heart
Regulation of RNA splicing in heart disease
Myotonic dystrophy
Hypertrophic cardiomyopathy
Dilated cardiomyopathy
Arrhythmias
Heart failure
Atherosclerosis
Congenital heart defects
Alternative splicing: Therapeutic potential
Conclusions and future perspectives
Acknowledgments
References
Chapter-9---Cardiac-transcriptomic-remodeling-_2021_Epigenetics-in-Cardiovas
Cardiac transcriptomic remodeling in metabolic syndrome
Oxidative stress in metabolic syndrome
Cardiovascular diseases and cardiac remodeling associated with the metabolic syndrome
Energy metabolism of the developing and diseased hearts
Remodeling of gene expression
How gene expression is controlled
Signal transduction in the failing heart
Regulation of gene expression and signaling pathway activity
Metabolic and stress-signaling pathways in the heart
Noncoding RNAs as controls of gene expression in HF
miRNAs in cardiac remodeling
Long noncoding RNAs in cardiac remodeling
The role of coronary microvascular inflammation in HFpEF
To metabolic syndrome
Conclusion
References
Chapter-10---Sex-differences-in-epigenetics-mech_2021_Epigenetics-in-Cardiov
Sex differences in epigenetics mechanisms of cardiovascular disease
Influence of sex in the development of cardiovascular diseases
Epigenetics and sex chromosomes at cardiovascular level
Epigenetics and sexual hormones at cardiovascular level
Mechanism of estrogen signaling
Mechanism of androgen signaling
Epigenetics and estrogen receptors
DNA methylation
Histone modification
Noncoding RNA
Epigenetics and androgen receptors
DNA methylation
Histone modification
Noncoding RNA
Conclusions and future directions
Acknowledgments
References
Chapter-11---Epigenetics-in-cardiac-development-an_2021_Epigenetics-in-Cardi
Epigenetics in cardiac development and human induced pluripotent stem cells
General introduction
Embryonic development of the heart
General principle
Epigenetic regulation in mammalian heart development
Models of cardiogenesis
Human induced pluripotent stem cells (hiPSCs)
General introduction
hiPSCs as models of epigenetics of cardiac development
hiPSCs reprogramming
Differentiation of hiPSCs into cardiomyocytes
Comparison of protocols
In vitro maturation of hiPSC-CMs
Future challenges
References
Chapter-12---Peripheral-blood-DNA-and-RNA-biomarker_2021_Epigenetics-in-Card
Peripheral blood DNA and RNA biomarkers of cardiovascular disease in clinical practice
Introduction
DNA mutations vs RNAs and epigenetic markers
Clinical need for DNA and RNA biomarkers
Requirements for implementation of good (epi)genomic biomarkers
Sample types and preanalytical variability
RNA biomarkers
Epigenetic DNA-based biomarkers
RNA biomarkers in cardiovascular disease
Putative RNA markers in discovery phase
RNAs in stable coronary artery disease
RNAs in heart transplantation
Epigenetic biomarkers in cardiovascular disease
DNA methylation and cardiovascular risk factors
DNA methylation and cfDNA in myocardial infarction and heart failure
Common CVD events and risk factor epigenetic biomarkers
Drug response prediction for personalized medicine
Limitations and future perspectives
References
Chapter-13---Epigenetics-and-physical-e_2021_Epigenetics-in-Cardiovascular-D
Epigenetics and physical exercise
Introduction
Cardiovascular adaptations to physical activity
The noncoding transcriptome and exercise
Noncoding RNAs as regulators of cardiovascular adaptations to exercise
Noncoding RNAs as regulators of the cardioprotective effects of exercise
Circulating noncoding RNAs and exercise
Noncoding RNAs as biomarkers of exercise
Effect of exercise on biomarkers with future application: Circulating miRNAs
Limitations and perspectives
Conclusions
Funding
References
Chapter-14---Long-noncoding-RNAs-and-circular-RN_2021_Epigenetics-in-Cardiov
Long noncoding RNAs and circular RNAs as heart failure biomarkers
Introduction
Long noncoding RNAs
Discovery and biogenesis
Functional classification
Circular RNAs
Discovery, biogenesis, and classification
Function
LncRNAs and circRNAs in cardiovascular biology
LncRNAs and circRNAs in cardiovascular development
LncRNA and circRNA landscape in heart failure
LncRNAs and circRNAs as biomarkers for heart failure
LncRNAs and circRNAs as therapeutic targets for heart failure
Translational medicine
Challenges and next steps
Conclusions
Acknowledgments
References
Chapter-15---Artificial-intelligence-in-clinical-decisi_2021_Epigenetics-in-
Artificial intelligence in clinical decision-making for diagnosis of cardiovascular disease using epigenetics ...
Introduction
Machine learning
Overview of the machine learning workflow
Feature engineering and data set creation
Handling missing data
Heterogeneous data and data integration
Feature selection and dimensionality reduction
Performance evaluation
Imbalanced classes
Machine learning algorithms
Supervised learning
Support vector machines
Artificial neural networks
Random forest
Unsupervised learning
Semisupervised learning
Ensemble methods
Deep learning
Machine learning applications
Application of machine learning in cardiology
Image processing
Risk factor determination and disease prediction
Application of machine learning using epigenetic data
Prediction of the epigenome
Histone modifications
Application of machine learning in diagnosis of cardiovascular disease using epigenetic mechanisms
Limitations
Conclusions
References
Chapter-16---Therapeutic-strategies-for-modulating-_2021_Epigenetics-in-Card
Therapeutic strategies for modulating epigenetic mechanisms in cardiovascular disease
RNA as a therapeutic target
Targeting epigenetics
Small-molecule epigenetic drugs
Oligonucleotides
MicroRNAs
Therapeutic utility of oligonucleotides
Oligonucleotide classes
Synthetic oligonucleotide chemistry
Oligonucleotide drugs in the cardiovascular field
Antisense and siRNA oligonucleotides for treatment of cardiovascular diseases
Antagomirs for cardiovascular pharmacotherapies
Challenges that need to be addressed
Nanoparticle delivery
Targeted delivery via bioconjugation
Other delivery approaches
Drug safety and off-target effects
Conclusion
References
Chapter-17---Single-cell-RNA-sequencing-in-ca_2021_Epigenetics-in-Cardiovasc
Single-cell RNA sequencing in cardiovascular science
Introduction
Basic principles
Current single-cell RNA-sequencing technologies
Single-cell RNA-sequencing data analysis
Single-cell RNA-sequencing strategy to evaluate the noncoding transcriptome
Recent applications of scRNA-seq to characterize the cardiovascular system
The developing heart
The adult heart
The vasculature
Publicly available resources
Programming and reprogramming
Futures developments
Acknowledgment
References
Chapter-18---Good-laboratory-and-experimental-practi_2021_Epigenetics-in-Car
Good laboratory and experimental practices for microRNA analysis in cardiovascular research
MicroRNAs as potential biomarkers in cardiovascular diseases
Good laboratory practices when studying circulating miRNAs for cardiovascular diseases
The workflow of determination of circulating miRNA levels using qRT-PCR
Standard operating procedures
Good practices for blood collection and handling
Good practices for serum/plasma recovery
Long-term storage of biological samples
Good recovery of archival sample practices
Good qRT-PCR practices to minimize contamination
Quality assessment of circulating miRNA analysis
Good experimental practices when studying circulating miRNAs for cardiovascular diseases
Always use the same blood fraction and collection tube for miRNA analysis
Always use the same miRNA extraction method/kit in a study
Detection methods and normalization strategies
Conclusions
References
Chapter-19---Analytical-challenges-in-microRNA-biomarke_2021_Epigenetics-in-
Analytical challenges in microRNA biomarker development: Best practices for analyzing microRNAs in cell-free ...
The promises and challenges of cell-free microRNA biomarkers
Common sources of preanalytical variability during miRNA analysis in cell-free biofluids
Sample type
Sample quality
Sample collection tubes
Sample processing conditions
Sample stability
Sources of analytical variability: RT-qPCR and NGS
RNA Extraction
Spike-in controls
RT-qPCR analysis of cell-free miRNAs
RT-qPCR assay validation for analysis of cell-free miRNAs
NGS analysis of cell-free miRNAs
Sources of biological variance
Conclusion
References
Chapter-20---Concept-of-biological-reference-materi_2021_Epigenetics-in-Card
Concept of biological reference materials for RNA analysis in cardiovascular disease
Introduction
Clinical and biological context
Production of RMs
Biobanking
Processing: Required documentation
Purity assessment
Homogeneity assessment
Stability assessment
Nominal value assignment and characterization
Complementary characterization
Confidence in the nominal values
Fitness for purpose
Outlook
Acknowledgment
References
Chapter-21---Unbiased-bioinformatics-analysis-of-micro_2021_Epigenetics-in-C
Unbiased bioinformatics analysis of microRNA transcriptomics datasets and network theoretic target prediction
Why do we need unbiased, omics-, and bioinformatics-based approaches in cardiovascular biology?
Three decades of unsuccessful clinical translation of cardioprotective approaches
Possible solutions for the repeated failures of clinical translation
A parsimonious transcriptomics approach by microRNA fingerprinting
microRNAs
Posttranscriptional regulation of gene expression by small noncoding RNAs
microRNA-target interaction databases
Transcriptomics techniques
DNA microarrays
NanoString nCounter
RNA-sequencing
Bioinformatics methodologies for unbiased target prediction
Concise introduction to network theoretic concepts
Network visualization
Network-based approaches for the analysis of omics datasets
Network theoretic analysis of microRNA expression profiles
Examples of successfully applying unbiased, microRNA transcriptomics-based methodologies
Conclusions and future perspectives
Acknowledgments
References
Conclusions-and-perspectives--The-present-and-futur_2021_Epigenetics-in-Card
Conclusions and perspectives: The present and future of epigenetics in cardiovascular disease
Acknowledgments
References
Index_2021_Epigenetics-in-Cardiovascular-Disease
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