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Global Translational Medicine Epigenetics on cardiovascular diseases

for miRNA-217 inhibitors in CVDs . Atherosclerosis has miRNA-based drugs have progressed significantly into
[92]
been shown to decrease following the regulation of specific preclinical and clinical testing. While there is insufficient
genes at the transcriptional or post-transcriptional level, appreciation for the role of miRNAs in the pathophysiology
with DNA methylation playing a role in ceasing relative of CVDs, a substantial number of deregulated or disease-
gene expression . Yang et al. identified microRNA-216a modified miRNAs exist, raising the question of whether
[93]
[94]
as an inducer of endothelial senescence and inflammation, the deregulation of a miRNA causes disease or merely
acting as an inhibitor of the Smad3/IκBα pathway and indicates it . Despite GWAS identifying polymorphisms
[83]
proposing it as a novel biomarker for elderly individuals in miRNA biogenesis factors, miRNA genes, and 3’
with atherosclerotic diseases. Plasma levels of miRNA- untranslated region variants (3’UTRs) strongly associated
216a were higher in older CAD patients, correlating with a with human traits and diseases, pathophysiological
31% increased risk compared to healthy controls. changes have been determined only in a few cases [103] . In

Chen et al. found that elevated levels of circulating a recent review, Maries et al. [104] summarize the current
[95]
miRNA-17-5p could serve as a diagnostic biomarker updates on the molecular mechanisms of over 30 miRNAs
for atherosclerosis. Li et al. evaluated the prospect of involved in post-myocardial infarction (MI) replacement
[96]
circulating miRNAs as biomarkers for atherosclerotic fibrosis leading to left ventricular remodeling and HF.
plaque rupture in stable CAD patients undergoing Extracellular vesicles (microparticles), produced by
percutaneous coronary intervention with a single stent human coronary artery smooth muscle cells, carry a variety
implantation. They identified three miRNAs, miR-155-5p, of miRNAs, such as miR-21-5p, miR-143-3p, miR-145-5p,
miR-483-5p, and miR-451a, as potential biomarkers for the miR-221-3p, and miR-222-3p, with some of these miRNAs
early detection of plaque rupture . Mao et al. examined originating from atherosclerotic plaques [105] . Exosomes,
[97]
[96]
genes with differential expressions in earlier and older small extracellular vesicles that transport regulatory
atherosclerotic plaques. Analyzing two public datasets miRNAs, mRNAs, and lncRNAs, function as intercellular
from the Gene Expression Omnibus (GEO) databases, messengers and information transmitters. Vaskova
they identified a total of 23 miRNAs, with miR-19A, miR- et al. [106] examined the effects on exosome production
19B, miR-126, and miR-155 standing out as potential employing a chronic rodent myocardial injury model
biomarkers for carotid atherosclerosis . and confirmed that miR-181a antagomiR has a beneficial
[97]
effect on cardiac function. Importantly, rats treated with
(b) miRNAs in CVDs
miR-181a antagomiR displayed a noticeable recovery
MiRNAs emerge as important regulators of homeostasis in in left-ventricular function and cardiac remodeling.
various organ systems, particularly in the cardiovascular Consequently, miR-181a could serve as a valuable early
system. Beyond their involvement in the CVD progression biomarker of myocardial ischemia, and its downregulation
process, such as cardiac hypertrophy and myocardial by a specific antagomiR holds potential for therapeutic
cell fibrosis, they also serve as promising therapeutic implementations [106] . MiR-144 has demonstrated protective
targets [98,99] . Myocardial implications in CVDs arise from effects against detrimental post-MI remodeling in both
disturbances in intracellular signaling across various cell ischemia and reperfusion and non-reperfused MI mouse
types, including VSMCs, endothelial cells, cardiomyocytes, models [107] .
and fibroblasts. Disturbances in intracellular signaling In an MI mouse model with a permanently ligated
cascades affect heterocellular communication, highlighting left anterior descending (LAD), miR-19a/19b prevented
the importance of identifying dysregulated miRNAs post-infarction HF. Intracardiac injection of miR-19a
under pathological conditions [100] . However, more efforts or miR-19b mimics reduced the infarct site, preserved
are required to recognize irregular miRNAs responsible cardiac function in the post-infarct period, and increased
for the clinical understanding of atherosclerosis, cardiac [108]
hypertrophy, and complex CVDs [100] . MiRNAs possess survival .
the unique ability to simultaneously regulate multiple In a porcine LAD occlusion MI model, the delivery of
elements within relevant pathways, making them potential miR-199a into the left ventricular led to significant cardiac
biomarkers and therapeutic targets [101,102] . Laggerbauer and function recovery, decreased infarct size, and reduced
Engelhardt reported on the advances in the identification cardiac fibrosis. Nevertheless, long-term expression
[83]
and characterization of miRNAs as therapeutic targets of miR-199a resulted in sudden cardiac death for the
in the cardiovascular system, discussing challenges majority of treated animals. This highlights the need for a
and prospects for clinical translation and application. more precise and constrained dosing and delivery strategy
The role of miRNAs in CVDs operates within a realm for any miRNA-based substances in clinical settings [109] .
with limitations of conventional pharmacotherapy, and The prospect of therapy for presently incurable diseases

Volume 2 Issue 4 (2023) 9 https://doi.org/10.36922/gtm.1868