Epigenetic Programming and Risk: The Birthplace of Cardiovascular Disease?

Vinci, Maria; Polvani, Gianluca; Pesce, Maurizio

doi:10.1007/s12015-012-9398-z

Cited by 28 publications

(23 citation statements)

References 172 publications

(177 reference statements)

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“…22 The importance of DNA methylation has been shown, for example, for the (dys)regulation of inducible nitric oxide synthase, whereas specific histone modifications have been identified that are involved in the fixation of proinflammatory gene expression patterns in diabetic disease models. 31 Platelet function also seems to be crucially dependent on physiological epigenetic imprinting. 32 All these processes are among the mechanisms considered important in smokingassociated cardiovascular pathology.…”

Section: Epigenetics Of Tobacco-associated Cardiovascular Diseasementioning

confidence: 99%

Current Genetics and Epigenetics of Smoking/Tobacco-Related Cardiovascular Disease

Breitling¹

2013

ATVB

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Abstract-Genetic and epigenetic factors are of great importance in cardiovascular biology and disease. Tobacco-smoking, one of the most important cardiovascular risk factors, is itself partially determined by genetic background and is associated with altered epigenetic patterns. This could render the genetics and epigenetics of smoking-related cardiovascular disease a textbook example of environmental epigenetics and modern approaches to multimodal data analysis. A pronounced association of smoking-related methylation patterns in the F2RL3 gene with prognosis in patients with stable coronary heart disease has recently been described. Nonetheless, surprisingly little concrete knowledge on the role of specific genetic variants and epigenetic modifications in the development of cardiovascular diseases in people who smoke has been accumulated. Beyond the current knowledge, the present review briefly outlines some chief challenges and priorities for moving forward in this field. variation in antioxidative resilience seems to have no clinical cardiovascular consequences by itself, but-in interaction with the excessive oxidative stress caused by smoking-it means that smoking-associated cardiovascular risks are much greater in ε4 carriers than in other subjects. 10 It has been realized that such gene-environment interactions could also interfere with the performance of lipid-lowering drugs, but the extent of this potentially far-reaching problem still needs to be clarified. 11Given the multitude of physiological phenomena involved in tobacco-smoking-related cardiovascular disease (ref. 12 for an informative overview), it is hardly surprising that similar interactions with smoking have been reported for sequence variants in candidate genes coding for proteins as diverse as lipoprotein lipase and interleukin-6, 10 prothrombotic mutations like factor II G20210A, 13 or transforming growth factor-β1.14 One study investigating an interaction of interleukin-18 polymorphisms with smoking regarding cardiovascular disease risk was exceptional for its laudable collaborative design emphasizing statistical power.15 Nonetheless, the level of evidence for the vast majority of currently suggested gene-smoking interactions ultimately remains very limited. The evolution of findings concerning an interaction between tobacco-smoking and variants in glutathione S-transferase genes with respect to cardiovascular disease risk-which started out as a seemingly plausible effect modification supported by multiple lines of evidence 8 and was further sugested later meta-analysis, 16 only to vanish with subsequent sample size escalation 17 -should be taken as a reminder of the danger of prematurely overinterpreting gene-smoking interactions or even higher order interactions (eg, gene-age-smoking). 18Thorough replication and follow-up studies need to become more of a norm in this statistically challenging field. A New Era of EpigeneticsStudies on epigenetic aspects of health and disease have exploded in recent years, mainly because of technological a...

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Section: Epigenetics Of Tobacco-associated Cardiovascular Diseasementioning

confidence: 99%

Current Genetics and Epigenetics of Smoking/Tobacco-Related Cardiovascular Disease

Breitling¹

2013

ATVB

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“…The responses of cells to mechanical cues have emerged as a general component of the chronic evolution of cardiovascular diseases and aging [22], a process with an important epigenetic component [23]. Taken together, these data suggest a tight relationship between the mechanosensitivity of CFs and downstream profibrotic cell signaling.…”

Section: Introduction: Relevance Of Cell Mechanics In Cardiac Fibrosismentioning

confidence: 89%

Cell-Based Mechanosensation, Epigenetics, and Non-Coding RNAs in Progression of Cardiac Fibrosis

Ferrari

Pesce

2019

IJMS

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The heart is par excellence the ‘in-motion’ organ in the human body. Compelling evidence shows that, besides generating forces to ensure continuous blood supply (e.g., myocardial contractility) or withstanding passive forces generated by flow (e.g., shear stress on endocardium, myocardial wall strain, and compression strain at the level of cardiac valves), cells resident in the heart respond to mechanical cues with the activation of mechanically dependent molecular pathways. Cardiac stromal cells, most commonly named cardiac fibroblasts, are central in the pathologic evolution of the cardiovascular system. In their normal function, these cells translate mechanical cues into signals that are necessary to renew the tissues, e.g., by continuously rebuilding the extracellular matrix being subjected to mechanical stress. In the presence of tissue insults (e.g., ischemia), inflammatory cues, or modifiable/unmodifiable risk conditions, these mechanical signals may be ‘misinterpreted’ by cardiac fibroblasts, giving rise to pathology programming. In fact, these cells are subject to changing their phenotype from that of matrix renewing to that of matrix scarring cells—the so-called myo-fibroblasts—involved in cardiac fibrosis. The links between alterations in the abilities of cardiac fibroblasts to ‘sense’ mechanical cues and molecular pathology programming are still under investigation. On the other hand, various evidence suggests that cell mechanics may control stromal cells phenotype by modifying the epigenetic landscape, and this involves specific non-coding RNAs. In the present contribution, we will provide examples in support of this more integrated vision of cardiac fibrotic progression based on the decryption of mechanical cues in the context of epigenetic and non-coding RNA biology.

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“…In particular, cells cultured in contact with high stiffness substrates appear the gene expression setting acquired in the stiff environment, even after shifting into a soft environment. Thus, similar to the so-called epigenetic memory associated with the exposure of cells to altered metabolic conditions (e.g., hyperglycemia) [47], tissue mechanics could also irreversibly affect the expression of pathology-related genes, even after reversion of matrix mechanics to normal conditions. In keeping with this hypothesis, there is the finding that migratory epithelial cells primed on hard ECM for a defined duration migrate faster and display higher actomyosin expression compared to controls even when in contact with a softer matrix [48].…”

Section: Role Of Mechanical Factors In Myofibroblast Activation and Cmentioning

confidence: 99%

Mechanotransduction in the Cardiovascular System: From Developmental Origins to Homeostasis and Pathology

Garoffolo

Pesce

2019

Cells

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With the term 'mechanotransduction', it is intended the ability of cells to sense and respond to mechanical forces by activating intracellular signal transduction pathways and the relative phenotypic adaptation. While a known role of mechanical stimuli has been acknowledged for developmental biology processes and morphogenesis in various organs, the response of cells to mechanical cues is now also emerging as a major pathophysiology determinant. Cells of the cardiovascular system are typically exposed to a variety of mechanical stimuli ranging from compression to strain and flow (shear) stress. In addition, these cells can also translate subtle changes in biophysical characteristics of the surrounding matrix, such as the stiffness, into intracellular activation cascades with consequent evolution toward pro-inflammatory/pro-fibrotic phenotypes. Since cellular mechanotransduction has a potential readout on long-lasting modifications of the chromatin, exposure of the cells to mechanically altered environments may have similar persisting consequences to those of metabolic dysfunctions or chronic inflammation. In the present review, we highlight the roles of mechanical forces on the control of cardiovascular formation during embryogenesis, and in the development and pathogenesis of the cardiovascular system.In the present contribution, we will focus on the role of mechanical forces in controlling the morphogenesis of the cardiovascular system and on their new emerging role as a pathology determinant. We will also describe how traction forces exerted locally by single cells or forces (e.g., laminar/perturbed shear stress, constant/oscillatory pressure) propagated passively in the tissues are converted into signals regulating intracellular biochemistry and gene expression underlying pathology progression. Definition of Cell Mechanotransduction: Outside-In and Inside-Out Communication in the Complex 3D Environment Similar to classical ligand/receptor interactions, mechanotransduction requires binding of cell surface receptors to their ligands immobilized into the extracellular matrix (ECM), or expressed at the surface of adjacent cells. Differences in the mechanical features of the ECM, or in the geometrical arrangement of receptor binding motifs, can have a direct readout on cell proliferation, differentiation and migratory responses. Mechanical cues are converted into biochemical signals by activation of intracellular cascades transmitted via the cytoskeleton and their components, for example the acto-myosin 'stress' fibers [4], the microtubules [5], the scaffolding proteins [6], and various kinases and phosphatases [7] (Figure 1). Cells 2019, 8, x 2 of 18asymmetric cellular divisions and establishment of initial embryonic polarity. Thereafter, the mechanotransduction process continues in adult life, contributing to tissue growth, homeostasis and, finally, disease programming. In the present contribution, we will focus on the role of mechanical forces in controlling the morphogenesis of the cardiovascular system and on...

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Epigenetic Programming and Risk: The Birthplace of Cardiovascular Disease?

Cited by 28 publications

References 172 publications

Current Genetics and Epigenetics of Smoking/Tobacco-Related Cardiovascular Disease

Current Genetics and Epigenetics of Smoking/Tobacco-Related Cardiovascular Disease

Cell-Based Mechanosensation, Epigenetics, and Non-Coding RNAs in Progression of Cardiac Fibrosis

Mechanotransduction in the Cardiovascular System: From Developmental Origins to Homeostasis and Pathology

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