f7e3849a50e4bfb80625bd5c8c4544df 267178.pdf 0dea6c42ae6ee0c8a79fa055ba22a865bf4af972 267178.pdf a6341fb4b46a79c957395ffcd77d169f083fa48b9cc6fcdc3a01a5f8720f18da 267178.pdf Title: Epigenetic Regulation by microRNAs in Hyperhomocysteinemia-Accelerated Atherosclerosis Subject: Increased serum levels of homocysteine (Hcy) is a risk factor for cardiovascular disease and is specifically linked to various diseases of the vasculature such as atherosclerosis. 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. Keywords: hyperhomocysteinemia; microRNAs; endothelial cells; macrophages; vascular smooth muscle cells and atherosclerosis Author: Raquel Griñán, Joan Carles Escolà-Gil, Josep Julve, Sonia Benítez and Noemí Rotllan Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Oct 18 09:28:00 2022 CEST ModDate: Tue Oct 18 09:32:20 2022 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 13 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1060366 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- OTZEDH+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 TOXVYJ+VnURWPalladioL Type 1 Custom yes yes no 15 0 ZGFJCN+URWPalladioL-Bold Type 1 Custom yes yes no 19 0 LGLKPQ+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 OXGKWO+URWPalladioL-Ital Type 1 Custom yes yes no 28 0 KESBIZ+EURM10 Type 1 Builtin yes yes no 32 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 50 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 53 0 XCUBZO+CMSY10 Type 1 Builtin yes yes no 78 0 HHKJJM+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 89 0 HHKJJN+PalatinoLinotype CID TrueType Identity-H yes yes yes 92 0 HHKJJO+PalatinoLinotype TrueType WinAnsi yes yes no 98 0 HHKJKA+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 101 0 HHKNKJ+Symbol Type 1C Custom yes yes yes 130 0 HHKJJM+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 135 0 HHKJJN+PalatinoLinotype CID TrueType Identity-H yes yes yes 138 0 HHKJJO+PalatinoLinotype TrueType WinAnsi yes yes no 144 0 HHKJKA+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 147 0 UJUUJI+PazoMath Type 1 Builtin yes yes no 155 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-06-21 02:32:24 CEST RepresentationInformation: 267178.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-06-20 15:39:19 CEST Size: 1060366 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 405 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Children: Item: Title: Homocysteine Biosynthesis and Catabolism Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Item: Title: Hyperhomocysteinemia as a Risk Factor in CVD Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Atherosclerosis-Related Hyperhomocysteinemia Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Epigenetic Regulation of Hyperhomocysteinemia-Related Atherosclerosis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Target Therapies in HHcy-Related Atherosclerosis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Info: Title: Epigenetic Regulation by microRNAs in Hyperhomocysteinemia-Accelerated Atherosclerosis Author: Raquel Griñán, Joan Carles Escolà-Gil, Josep Julve, Sonia Benítez and Noemí Rotllan Subject: Increased serum levels of homocysteine (Hcy) is a risk factor for cardiovascular disease and is specifically linked to various diseases of the vasculature such as atherosclerosis. 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. 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