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Global Translational Medicine Epigenetics on cardiovascular diseases

the regulation of DNMTs . In the quest for potential 3.2. Histone modifications
[21]
biomarkers, DNA methylation microarray analyses were Histone modifications constitute epigenetic regulatory
conducted to uncover CpG methylation profiles during the mechanisms that act on histone tails through processes
atherosclerotic process in the human aorta and in human such as methylation, acetylation, phosphorylation,
cells [55-58] . The upregulation of DNMT1 by LDL cholesterol, adenylation, ubiquitination, and adenosine diphosphate
leading to the methylation and repression of the Krüppel- ribosylation . These post-translational changes play
[21]
like factor 2 gene (KLF2) promoter, results in endothelial a crucial role in remodeling chromatin structure and
dysfunction. Simultaneously, the upregulation of DNMT3a
in human aortic endothelial cells induces methylation regulating gene expression by influencing chromatin
and repression of the Krüppel-like factor 4 gene (KLF4) accessibility, representing the most extensive group of
[56,66]
promoter, contributing to regional atherosclerosis [59,60] . chromatin modifications identified to date . The
Furthermore, DNA methylation and hydroxymethylation regulatory impact of histone modifications extends to
were identified in blood mononuclear cells from elderly observed cellular functions, suggesting that histone analysis
patients with CAD, showing a correlation with the severity holds significant potential as the missing bridge between
of coronary atherosclerosis . genomics and proteomics. Alterations in chromatin
[61]
conformation can be linked to modifications in gene
Zhang and Zeng propose that environmental factors expression and, consequently, phenotype . The reliability
[62]
[67]
play a critical role in shaping the epigenetic trait of genes of histone analysis for identification and quantification
without altering the DNA sequence, leading to significant is speculated to be high, paving the way for its potential
repercussions on cellular performance. Furthermore, they incorporation as a routine method in SB. Integrating
suggest that abnormal DNA methylation disrupts the histone mass spectrometry results with genomics and
transcription and expression of critical regulatory genes, proteomics datasets could enhance the comprehensiveness
resulting in the development of a proatherogenic cellular of SB methodologies .
[67]
phenotype. This phenotype manifests as endothelial cell
dysfunction, abnormal VSMC proliferation, extracellular Endothelial-mesenchymal transition (EndMT) is a
matrix formation, and inflammation in CVDs. cellular differentiation activity where endothelial cells
undergo a change in their functional or phenotypical type,
In another study, Zhang et al. employed bibliometric acquiring mesenchymal-like characteristics that contribute
[63]
and visual methods to unravel scientific areas and trends in to the formation and development of atherosclerotic
CVDs, aiming to anticipate the direction of future research plaques. While numerous studies have implicated EndMT
in epigenetics. Notably, there have been limited bibliometric in myocardial fibrosis, myocardial hypertrophy, and
studies in this subject area to date. Their analysis, based on hypertension, the molecular mechanisms motivating
the Web of Science Core Collection, identified a total of EndMT are still in the preliminary stage. Jun et al.
[68]
2,617 publications related to DNA methylation in CVDs. emphasize the role of histone modifications in EndMT
The United States of America, China, and England were
the top three countries contributing to the field of DNA in CVDs, targeting histone-modifying enzymes for CVD
[69]
methylation. therapy. Lecce et al. specifically recognize histone
deacetylation, mediated by HDAC9, as a contributor to
Palou-Marquez et al. designed a study to integrate both EndMT and atherosclerosis. In mice, Hdac9 knockout
[64]
DNA methylation and gene expression data, aiming to resulted in decreased EndMT and a limited plaque area. This
identify biomarkers associated with CVDs risk. They highlights the connection of HDAC9 to vascular pathology
retrieved data from the Framingham Offspring Study, by influencing EndMT and establishes a pathological link
a cohort study with data on DNA methylation and between EndMT, HDAC9, and atherosclerosis. Targeting
gene expression. Four independent factors related to HDAC9 may prove beneficial for stabilizing plaques and
inflammation, endothelium homeostasis, visceral fat, slowing the progression of atherosclerotic disease .
[69]
cardiac remodeling, and lifestyles were identified as Conversely, HDAC3 appears to have a protective result
contributors to the determination of cardiovascular risk. in apolipoprotein E deficient (apoE−/−) mice. HDAC3
[65]
In a similar vein, Fernandez-Sanles et al. sought preserves endothelial integrity, and its insufficiency
[70]
to identify differentially methylated loci associated induces atherosclerosis . The expression of HDACs is
with AMI and assess their validity as predictive and upregulated when the aortic VSMCs are stimulated. On
causal biomarkers. They recognized 34 CpGs related the other hand, the repression of HDACs reduces aortic
to AMI, shedding light on the significance of smoking, VSMC proliferation by altering gene expression, providing
[72]
lipid metabolism, and inflammation in the biological protection against atherosclerosis . Greibel et al.
[71]
mechanisms related to AMI. described an increase in histone acetylation on H3K9 and
Volume 2 Issue 4 (2023) 7 https://doi.org/10.36922/gtm.1868