16ff241d10aa5f44520d9f8ce2dc7888 ijms-25-03433.pdf 76ba1b727ca9062da7bc585b5c3f8d1d56d2c818 ijms-25-03433.pdf 0014c4c3cb1e5bd3dd1ed5d968ad4aac18e2f4d86fabbeec099574d44abc2290 ijms-25-03433.pdf Title: The Role of Epigenetics in Brain Aneurysm and Subarachnoid Hemorrhage: A Comprehensive Review Subject: This comprehensive review explores the emerging field of epigenetics in intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (aSAH). Despite recent advancements, the high mortality of aSAH needs an understanding of its underlying pathophysiology, where epigenetics plays a crucial role. This review synthesizes the current knowledge, focusing on three primary epigenetic mechanisms: DNA methylation, non-coding RNA (ncRNA), and histone modification in IA and aSAH. While DNA methylation studies are relatively limited, they suggest a significant role in the pathogenesis and prognosis of IA and aSAH, highlighting differentially methylated positions in genes presumably involved in these pathologies. However, methodological limitations, including small sample sizes and a lack of diverse population studies, temper these results. The role of ncRNAs, particularly miRNAs, has been more extensively studied, but there are still few studies focused on histone modifications. Despite methodological challenges and inconsistent findings, these studies underscore the involvement of miRNAs in key pathophysiological processes, including vascular smooth muscle regulation and the inflammatory response. This review emphasizes methodological challenges in epigenetic research, advocating for large-scale epigenome-wide association studies integrating genetic and environmental factors, along with longitudinal studies. Such research could unravel the complex mechanisms behind IA and aSAH, guiding the development of targeted therapeutic approaches. Keywords: subarachnoid hemorrhage; intracranial aneurysm; epigenetics; DNA methylation; microRNA; circular RNA; long non-coding RNA Author: Isabel Fernández-Pérez, Adrià Macias-Gómez, Antoni Suárez-Pérez, Marta Vallverdú-Prats, Eva Giralt-Steinhauer, Lidia Bojtos, Sílvia Susin-Calle, Ana Rodriguez-Campello, Daniel Guisado-Alonso, Joan Jimenez-Balado, Jordi Jiménez-Conde and Elisa Cuadrado-Godia Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Fri Aug 23 10:56:45 2024 CEST ModDate: Fri Aug 23 10:57:22 2024 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 25 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1057295 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- UQZHSH+VnURWPalladioL-Bold Type 1 Custom yes yes yes 10 0 MCAOPI+URWPalladioL-Bold Type 1 Custom yes yes yes 16 0 FCAHTK+URWPalladioL-Roma Type 1 Custom yes yes yes 22 0 RKZWVW+URWPalladioL-Ital Type 1 Custom yes yes yes 27 0 YWQWLZ+VnURWPalladioL Type 1 Custom yes yes yes 32 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 48 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 51 0 AOPHAZ+CMSY10 Type 1 Builtin yes yes yes 71 0 MBBBKC+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 122 0 MBBBLC+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 128 0 MBBCDA+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 134 0 MBBCDB+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 140 0 MBBCDC+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 143 0 MBBCDD+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 146 0 MBBCEE+PalatinoLinotype-Roman TrueType MacRoman yes yes no 149 0 LWLIVD+EURM10 Type 1 Builtin yes yes yes 170 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-10-31 02:39:37 CET RepresentationInformation: ijms-25-03433.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-10-30 17:42:07 CET Size: 1057295 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 612 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Overview of Epigenetics and Its Mechanisms Destination: section.2 Children: Item: Title: DNA Methylation (DNAm) Destination: subsection.2.1 Item: Title: Non-Coding RNA Molecules (ncRNAs) Destination: subsection.2.2 Children: Item: Title: MicroRNAs Destination: subsubsection.2.2.1 Item: Title: Long Non-Coding RNAs Destination: subsubsection.2.2.2 Item: Title: Circular RNAs Destination: subsubsection.2.2.3 Item: Title: Histone Modification Destination: subsection.2.3 Item: Title: Results Destination: section.3 Children: Item: Title: DNA-Methylation Destination: subsection.3.1 Item: Title: Non-Coding RNA Destination: subsection.3.2 Children: Item: Title: MicroRNA Destination: subsubsection.3.2.1 Item: Title: Long Non-Coding RNA Destination: subsubsection.3.2.2 Item: Title: Circular RNA Destination: subsubsection.3.2.3 Item: Title: Studies Based on Bioinformatic Analysis: Regulation of Gene Expression through Non-Coding RNA Destination: subsubsection.3.2.4 Item: Title: Histone Modification Destination: subsection.3.3 Item: Title: Discussion Destination: section.4 Children: Item: Title: Epigenetic Mechanisms and Implications Destination: subsection.4.1 Item: Title: Limitations Destination: subsection.4.2 Item: Title: Future Directions Destination: subsection.4.3 Item: Title: Materials and Methods Destination: section.5 Item: Title: Conclusions Destination: section.6 Item: Title: References Destination: section.7 Info: Title: The Role of Epigenetics in Brain Aneurysm and Subarachnoid Hemorrhage: A Comprehensive Review Author: Isabel Fernández-Pérez, Adrià Macias-Gómez, Antoni Suárez-Pérez, Marta Vallverdú-Prats, Eva Giralt-Steinhauer, Lidia Bojtos, Sílvia Susin-Calle, Ana Rodriguez-Campello, Daniel Guisado-Alonso, Joan Jimenez-Balado, Jordi Jiménez-Conde and Elisa Cuadrado-Godia Subject: This comprehensive review explores the emerging field of epigenetics in intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (aSAH). Despite recent advancements, the high mortality of aSAH needs an understanding of its underlying pathophysiology, where epigenetics plays a crucial role. This review synthesizes the current knowledge, focusing on three primary epigenetic mechanisms: DNA methylation, non-coding RNA (ncRNA), and histone modification in IA and aSAH. While DNA methylation studies are relatively limited, they suggest a significant role in the pathogenesis and prognosis of IA and aSAH, highlighting differentially methylated positions in genes presumably involved in these pathologies. However, methodological limitations, including small sample sizes and a lack of diverse population studies, temper these results. The role of ncRNAs, particularly miRNAs, has been more extensively studied, but there are still few studies focused on histone modifications. Despite methodological challenges and inconsistent findings, these studies underscore the involvement of miRNAs in key pathophysiological processes, including vascular smooth muscle regulation and the inflammatory response. This review emphasizes methodological challenges in epigenetic research, advocating for large-scale epigenome-wide association studies integrating genetic and environmental factors, along with longitudinal studies. Such research could unravel the complex mechanisms behind IA and aSAH, guiding the development of targeted therapeutic approaches. 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