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Epigenetic Modifications: Basic Mechanisms and Role in Cardiovascular Disease

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Handy, Diane E., Castro, Rita, Loscalzo, Joseph·2011·Circulation
DOI 10.1161/circulationaha.110.956839
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Abstract

The term epigenetics was first used to refer to the complex interactions between the genome and the environment that are involved in development and differentiation in higher organisms. Today, this term is used to refer to heritable alterations that are not due to changes in DNA sequence. Rather, epigenetic modifications, or tags, such as DNA methylation and histone modification, alter DNA accessibility and chromatin structure, thereby regulating patterns of gene expression. These processes are crucial to normal development and differentiation of distinct cell lineages in the adult organism. They can be modified by exogenous influences, and as such, they can contribute to or be the result of environmental alterations of phenotype or pathophenotype. Importantly, epigenetic programming has a crucial role in the regulation of pluripotency genes, which become inactivated during differentiation. Here, we review the major mechanisms in epigenetic regulation; highlight the role of stable, long-term epigenetic modifications that involve DNA methylation; and discuss those modifications that are more flexible (short-term) and involve histone modifications, such as methylation and acetylation. We will also discuss the role of nutritional and environmental challenges in generational inheritance and epigenetic modifications, concentrating on examples that relate to complex cardiovascular diseases, and specifically dissect the mechanisms by which homocysteine modifies epigenetic tags. Lastly, we will discuss the possibilities of modifying therapeutically acquired epigenetic tags, summarizing currently available agents and speculating on future directions. Chromatin is the complex of chromosomal DNA associated with proteins in the nucleus (for review, see Campos and Reinberg1). DNA in chromatin is packaged around histone proteins, in units referred to as nucleosomes. A nucleosome has 147 base pairs of DNA associated with an octomeric core of histone proteins, which consists of 2 H3-H4 histone dimers surrounded by 2 H2A-H2B dimers. N-terminal histone tails protrude from nucleosomes into the nuclear lumen. …

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Metadata

Authors
Handy, D. E., Castro, R., & Loscalzo, J.
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2011-05-17
Volume
123
Issue
19
Pages
2145-2156
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/circulationaha.110.956839
OpenAlex
W2077342495
Cited by
1,067
References
19
FWCI
7.88
Type
journal article
Language
en
Open access
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CoChat. (2026). Citation check: Epigenetic Modifications: Basic Mechanisms and Role in Cardiovascular Disease. https://app.cochat.ai/papers/10.1161/circulationaha.110.956839
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Handy, D. E., Castro, R., & Loscalzo, J. (2011). Epigenetic Modifications: Basic Mechanisms and Role in Cardiovascular Disease. Circulation. https://doi.org/10.1161/circulationaha.110.956839

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