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Global Translational Medicine Epigenetics on cardiovascular diseases

ranging from molecules to phenotypes and extending to remains limited. Similarly, personalized medicine and
encompass societal to environmental factors [29,40,41] . precision medicine have not gained widespread recognition
The holistic principle analyzes the structural in clinical applications, with a prevailing tendency toward
organization and regulation of networks with functional a reductionist clinical approach in the treatment of patients
properties, which “emerge” through a self-organized with complex CVDs. To advance beyond this, traditional
procedure complying with the foundations of a hierarchical medicine needs to advance into the era of network
multileveled system. In the context of clinical cardiology, medicine, aligning with the precision medicine paradigm
two interrelated holistic concepts in SB are pertinent: to improve our diagnostic and therapeutic capabilities
[47]
the emerging properties with an upward direction (with (Figure 3) .
upward constraints) and the proposal of constraint-
applied causation with a downward direction (downward 3. Epigenetic alterations in atherosclerosis
constraints) from the phenotype to epigenetic factors. and CVDs
(Figure 2) [12,29,42] . Epigenetic regulatory mechanisms encompass various
The holistic principle of downward (top-down) processes:
causation within the biological ladder, characterized (i) DNA methylation.
by an integrated systems view, stands in contrast to the (ii) Post-translational histone modifications on proteins:
reductionist approach, which conceptualizes biological Histone modifications, while not altering the DNA
reality as upward (bottom-up) causation. The holistic nucleotide sequence, can modify its availability to the
principle elucidates the inadequacy of relying solely on transcriptional apparatus.
bottom-up causation in the context of multi-level biology. (iii) Post-transcriptional regulation of gene expression by
Integrative network analysis and constraint-based thinking ncRNAs.
emerge as important tools for gaining a more profound
understanding of the intrinsic complexity of CVDs [12,43-45] . Epigenetic changes resulting from these mechanisms
can lead to the silencing, downregulation, or upregulation
The field of developmental biology was revolutionized [48]
through the advent of “omics” technology and Clustered of gene expression (Figure 4).
Regularly Interspaced Palindromic Repeats genome The majority of genetic diversity associated with a
engineering. These innovations have propelled disease is identified within non-coding areas of the genome,
biology toward holism, offering a new perspective on with epigenetics playing a regulatory role in a downward
development . Despite these strides, the integration direction. Cellular-based regulation of gene expression
[46]
of epigenetic biomarkers into routine medical practice during transcription and translation primarily occurs

Figure 2. Constraints and emergent properties are two concepts in systems biology that explain the interrelationship and interaction between higher
and lower levels of the biological ladder. Epigenetics encompass DNA methylation, histone, non-coding ribonucleic acids (ncRNAs), and environmental
exposures (Adopted from Lourida and Louridas with modifications).
[12]

Volume 2 Issue 4 (2023) 5 https://doi.org/10.36922/gtm.1868