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Global Translational Medicine                                        Epigenetics on cardiovascular diseases



            through the use of precision genetic or medical techniques   on lncRNAs, including sequences, transcriptome data, and
            is anticipated in the near future. Delivery of therapeutic   interactions with connected proteins or genes. It is important
            molecules in now inaccessible target tissues, such as the   to integrate data from various origins for the numerous
            cardiac infarct site, will soon be plausible. The main barrier   lncRNAs to specify functions and regulatory mechanisms.
            restraining the clinical implementation of miRNA-based   A  large number of lncRNAs have been identified as
            therapeutics is the focused, selected delivery to the infarct   significant regulators of cardiac development and aging,
            site [110,111] .                                   yet their pluripotent function in cardiac development
              Hong et al. [112]  proposed, for better miRNA delivery, an   and  disease,  along  with  their  diagnostic,  prognostic,  and
            anti-coagulative nanocomplex to carry and deliver a miR-1   therapeutic utility, remains to be determined [120] . Rezaee
            inhibitor capable of reducing microthrombus formation and   et al. [121]  outline the potential of various lncRNAs to serve
            microvascular obstruction and inhibiting blood-coagulation   as diagnostic, prognostic,  and therapeutic biomarkers  in
            factor Xa [112] . Bejerano et al. [113]  introduced a nanoparticle-  HF. In HF, various molecular mechanisms are markedly
            based delivery of a miR-21 mimic to cardiac macrophages at   deregulated by divergent lncRNAs. LncRNAs can influence
            the infarct site in a mouse ligation model as a new therapeutic   distinct signaling pathways by targeting molecules or
            strategy.  Feng and Tsao [114]   expressed their apprehension   cellular mechanisms, and changes in their expression are
            about the potential dangers of the systemic effects of its   observed in diverse types of CVDs and HF, supporting the
            miRNA mimics and suggested that any miRNA-based    notion that they play an important in the occurrence and
            substances are better used locally rather than systemically.   progression of heart diseases [121] .
            Bielska et al. [115]  attempted to uncover circulating miRNAs as   New biomarkers are crucial for improving early
            potential biomarkers for the early identification of CAD risk   detection and predicting the progression of AMI.
            in DM patients and discovered six miRNAs (miR-615-3p,   Wang  et al. [122]  evaluated the potential of the lncRNA
            miR-3147, miR-1224-5p, miR-5196-3p, miR-6732-3p, and   GAS6-AS1 in distinguishing AMI patients and predicting
            miR-548b-3p) that were overexpressed in the serum of   outcomes.  The  discriminative ability of  GAS6-AS1  in
            type 2 DM patients with CAD.                       identifying AMI patients was  evaluated using Kaplan–

              A substantial number of descriptive publications   Meier and Cox analysis and its association with critical
            on miRNAs await, pending critical evaluation for the   patient characteristics was assessed through Spearman’s
            identification and validation of the discovered miRNAs.   correlation analysis. The study concluded that decreased
            While thousands of papers are published annually linking   GAS6-AS1  expression  could  effectively  distinguish  AMI
            miRNAs to different genes and human diseases, only a   patients from healthy controls [122] .
            limited number delve into the molecular mechanisms of   VSMCs constitute a significant cell type within
            miRNAs. There is a pressing need for a greater emphasis
            on understanding the mechanisms underlying miRNAs,   atherosclerotic plaques, and their phenotypic transition
            and researchers seeking associations of specific miRNAs   gives rise to diverse cell categories within the plaques. In
            with biological phenotypes should shoulder a heightened   CVDs, the rapid proliferation and migration of VSMCs
            responsibility [116] .                             in the arterial wall contribute to the abnormal structure
                                                               and function of the arterial intima-middle layer. Shi
            3.3.2. Long non-coding ribonucleic acids           et  al. [123]  identified 4579 known and 13,655  de  novo
                                                               lncRNAs in human coronary artery VSMCs, highlighting
            LncRNAs regulate gene expression by altering chromatin   the crucial role of lncRNAs in the phenotypic transition
            structure and DNA accessibility; moreover, they enhance   of smooth muscle cells and human atherosclerotic disease.
            selectivity and control numerous cellular processes such as
            DNA methylation and histone modification [117,118] .  LncRNAs act as upstream regulators of cellular processes
                                                               associated with atherosclerosis, pulmonary hypertension,
              Belonging to a category of RNAs produced by RNA   and aneurysms – three lethal CVDs [124] . In general,
            polymerase II, lncRNAs play a key role in cell processes,   miRNAs and lncRNAs play essential roles in maintaining
            including transcription and regulation of gene expression.   physiological homeostasis by regulating the expression
            LncRNAs exhibit essential regulatory functions, interacting   of various genes. They also attract scientific interest as
            with proteins, other RNAs, and DNA. They also play a role   potential biomarkers for diagnosis and therapeutic targets
            in regulating biological processes related to vascular tissue   in DM and CVDs [125,126] .
            homeostasis, atherosclerotic lesion formation, and plaque
            destabilization [119] .                            3.3.3. Circular non-coding ribonucleic acids
              Thousands of lncRNAs need to be functionally     CircRNAs exert their regulatory functions through specific
            categorized, considering the abundance of genomic data   mechanisms: (i) acting as miRNA sponges, modulating


            Volume 2 Issue 4 (2023)                         10                       https://doi.org/10.36922/gtm.1868
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