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However, the precise mechanisms by which Hcy contributes to this condition remain elusive. During the development of atherosclerosis, epigenetic modifications influence gene expression. As such, epigenetic modifications are an adaptive response to endogenous and exogenous factors that lead to altered gene expression by methylation and acetylation reactions of different substrates and the action of noncoding RNA including microRNAs (miRNAs). Epigenetic remodeling modulates cell biology in both physiological and physiopathological conditions. DNA and histone modification have been identified to have a crucial role in the progression of atherosclerosis. However, the potential role of miRNAs in hyperHcy (HHcy)-related atherosclerosis disease remains poorly explored and might be essential as well. There is no review available yet summarizing the contribution of miRNAs to hyperhomocystein-mediated atherogenicity or their potential as therapeutic targets even though their important role has been described in numerous studies. Specifically, downregulation of miR-143 or miR-125b has been shown to regulate VSCMs proliferation in vitro. In preclinical studies, downregulation of miR-92 or miR195-3p has been shown to increase the accumulation of cholesterol in foam cells and increase macrophage inflammation and atherosclerotic plaque formation, respectively. Another preclinical study found that there is a reciprocal regulation between miR-148a\/152 and DNMT1 in Hcy-accelerated atherosclerosis. Interestingly, a couple of studies have shown that miR-143 or miR-217 may be used as potential biomarkers in patients with HHcy that may develop atherosclerosis. Moreover, the current review will also update current knowledge on miRNA-based therapies, their challenges, and approaches to deal with Hcy-induced atherosclerosis.<\/jats:p>","DOI":"10.3390\/ijms232012452","type":"journal-article","created":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T21:18:02Z","timestamp":1666127882000},"page":"12452","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Epigenetic Regulation by microRNAs in Hyperhomocysteinemia-Accelerated Atherosclerosis"],"prefix":"10.3390","volume":"23","author":[{"given":"Raquel","family":"Gri\u00f1\u00e1n","sequence":"first","affiliation":[{"name":"Institut d\u2019Investigaci\u00f3 Biom\u00e8dica Sant Pau (IIB SANT PAU), 08041 Barcelona, Spain"},{"name":"Departament de Bioqu\u00edmica i Biologia Molecular, Universitat Aut\u00f2noma De Barcelona, 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9021-2485","authenticated-orcid":false,"given":"Joan Carles","family":"Escol\u00e0-Gil","sequence":"additional","affiliation":[{"name":"Institut d\u2019Investigaci\u00f3 Biom\u00e8dica Sant Pau (IIB SANT PAU), 08041 Barcelona, Spain"},{"name":"CIBER de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6531-2246","authenticated-orcid":false,"given":"Josep","family":"Julve","sequence":"additional","affiliation":[{"name":"Institut d\u2019Investigaci\u00f3 Biom\u00e8dica Sant Pau (IIB SANT PAU), 08041 Barcelona, Spain"},{"name":"CIBER de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3565-0743","authenticated-orcid":false,"given":"Sonia","family":"Ben\u00edtez","sequence":"additional","affiliation":[{"name":"Institut d\u2019Investigaci\u00f3 Biom\u00e8dica Sant Pau (IIB SANT PAU), 08041 Barcelona, Spain"},{"name":"CIBER de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0587-8045","authenticated-orcid":false,"given":"Noem\u00ed","family":"Rotllan","sequence":"additional","affiliation":[{"name":"Institut d\u2019Investigaci\u00f3 Biom\u00e8dica Sant Pau (IIB SANT PAU), 08041 Barcelona, Spain"},{"name":"CIBER de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1136\/bmj.325.7374.1202","article-title":"Homocysteine and cardiovascular disease: Evidence on causality from a meta-analysis","volume":"325","author":"Wald","year":"2002","journal-title":"BMJ"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1056\/NEJMoa011613","article-title":"Plasma Homocysteine as a Risk Factor for Dementia and Alzheimer\u2019s Disease","volume":"346","author":"Seshadri","year":"2002","journal-title":"N. 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