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Global Translational Medicine                                        Epigenetics on cardiovascular diseases



            H3K27 in VSMCs from atherosclerotic lesions, correlating   regarding the standardization of collected samples from
            with  the  degree  of  plaque  damage.  Furthermore,  H3K9   pathology departments. Issues related to sample firmness,
            and H3K27 methylation were markedly decreased      magnitude, and coherence present challenges that need to
            in atherosclerotic plaques, further highlighting their   be addressed to ensure the reliability and applicability of
            association with disease severity . Yang et al.  emphasize   findings .
                                     [72]
                                                [73]
                                                                     [78]
            the importance of histone methylation and explore the
            effects of histone methyltransferases and demethylases   3.3.1. Small noncoding ribonucleic acids (microRNAs
            on  the  pathogenesis  of  CVDs.  They  also  discuss  the   or miRNAs)
            therapeutic potential of inhibitors of histone methylation   MiRNAs constitute a group of approximately 21-  to
            and demethylation in the context of CVDs.          25-nucleotide small RNAs that exert negative control
                                                               over gene expression at the post-transcriptional stage,
            3.3. Non-coding ribonucleic acids
                                                               significantly enhancing our understanding of complex
            The ncRNAs are transcribed from the genome and     gene regulatory networks . However, careful attention
                                                                                    [79]
            function at  the  RNA  level  without  being  translated into   is required, as miRNAs typically target multiple mRNAs
            proteins. Representing a diverse category of molecules,   from various genes, and each gene can be targeted
            ncRNAs play roles in cell proliferation, apoptosis, and   by multiple  miRNAs.  The complexity of this network
            metabolism . Their significance, especially in relation to   demands thorough scrutiny before a specific miRNA can be
                     [74]
            mRNA’s fundamental role in overseeing gene functioning,   considered a reliable biomarker for a disease . Extensive
                                                                                                   [80]
            has reshaped our understanding of cellular processes.   reviews have covered the biogenesis, identification,
            Epigenetic regulation relies on the mechanisms of ncRNAs,   mechanism of action, and degradation pathways of
            which vary in size from very small 22-nucleotide miRNAs   miRNAs [81,82] . While the operative number of miRNAs in
            to transcripts exceeding 200 nucleotides (lncRNA). These   humans ranges from 556 to 758, the functionally active
            molecules participate in translation and gene regulation,   ones expressed at adequately high levels in tissue are more
            with established communication between ncRNAs and   limited.  In  the  cardiovascular  system,  150  miRNAs  are
            other epigenetic factors. Furthermore, ncRNAs serve as   operative, and this number is further restricted to 30–35
            dominant  post-transcriptional  mechanistic  regulators   miRNAs in experimental  in vivo models [83-85] . MiRNAs
            of mRNA throughout all stages of atherosclerosis [2,75,76] .   regulate gene expression by inhibiting translation through
            The  emergence  of  epigenetic  biomarkers  in  CVDs   the repression or degradation of targeted mRNAs at the
            has revolutionized personalized medicine, enhancing   post-transcriptional level [86-88] . Dysregulated expression
            diagnostic and prognostic capabilities, and predicting   of miRNAs is associated with various cellular processes,
            the risk of future comorbidities . Within atherosclerotic   including hyperlipidemia, atherosclerosis, obesity, DM, and
                                     [52]
            lesions and circulation, specific ncRNAs or clusters   CVDs . In a study by Kong et al.  involving 326 patients
                                                                                         [89]
                                                                    [88]
            of ncRNAs have been identified as therapeutic targets   with DM and 342 healthy controls in a northern Chinese
            or biomarkers for atherosclerotic plaque progression.   Han population, the CC genotype of rs4705342 was found
            Clinicopathological discoveries, alongside studies in   to increase the expression of miRNA-143, potentially
            animal models, have elucidated the effects of ncRNAs   acting as a risk factor for DM. However, the relationship
            on the formation and progression of atherosclerosis .   between circulating and tissue miRNAs remains unclear,
                                                        [2]
            Macvanin  et al.  address the increasing prevalence of   as many surveys reveal that miRNA levels in the blood may
                         [77]
            diabetes mellitus (DM) and CVDs worldwide, highlighting   not accurately reflect alterations in tissue levels, given that
            numerous regulatory ncRNAs associated with these   miRNAs can also be produced by immune cells .
                                                                                                     [90]
            conditions. NcRNAs are also explored as prognostic
            biomarkers and potential therapeutic elements for DM and   (a) miRNAs in atherosclerosis
            CVDs.                                              MiRNAs hold promise as stable molecular biomarkers
              The  scientific  expertise  in  the  field  of  ncRNAs   and potential  drug targets,  with  modifications tailored
            encounters certain limitations, primarily stemming   to specific tissues or diseases.  However, the current
            from the absence of multicenter surveys with persuasive   literature lacks extensive records on miRNA expression
            verification for clinical applicability. The possibility of   in human atherosclerosis, and the role of miRNAs
            diverse formations containing various ncRNAs and other   in human atherosclerotic arteries remains largely
                                                                       [91]
            biomarkers suggested that, with the help of AI, more specific   undefined . In a mouse model featuring proatherogenic
            diagnostic and prognostic procedures for CVDs may be   apoE mice, the presence of miRNA-217 was associated
                                                                   -/- 
            developed . Selecting a cluster of biomarkers for a specific   with diminished nitric oxide production and increased
                    [48]
            CVD poses a challenge, compounded by uncertainties   endothelial dysfunction, suggesting therapeutic potential
            Volume 2 Issue 4 (2023)                         8                        https://doi.org/10.36922/gtm.1868
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