Epigenetics of cerebrovascular diseases: an update review of clinical studies
Creators: name: Ciaccio, Anna Maria
name: Tuttolomondo, Antonino
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Medicine
subject: Genetics
subject: FOS: Biological sciences
subject: Molecular Biology
subject: Neuroscience
subject: Environmental Sciences not elsewhere classified
subject: Biological Sciences not elsewhere classified
subject: Mental Health

description: Cerebrovascular diseases, especially stroke, are critical and heterogenous clinical conditions associated with high mortality and chronic disability. Genome-wide association studies reveal substantial stroke heritability, though specific genetic variants account for a minor fraction of stroke risk, suggesting an essential role for the epigenome. Epigenome-wide association studies and candidate gene approaches show that DNA methylation patterns significantly influence stroke susceptibility. Additionally, chromatin remodelers and non-coding RNA regulate gene expression in response to ischemic conditions. In this updated review, we summarized the progress of knowledge on epigenetics in the field of ischemic stroke underlying opportunities and challenges. Cerebrovascular diseases include different clinical conditions, with stroke being the most serious. Stroke is the second leading cause of death and the primary cause of long-term disability globally. It is a multifactorial condition resulting from the interaction among environmental, genetic and epigenetic factors. In the last decades, several authors have explored the role of epigenetics in stroke. Epigenetics involves changes in how our genes work without altering the actual DNA. Fundamental epigenetic mechanisms include DNA methylation, histone modifications, chromatin remodeling and RNA-based mechanisms. Among these, DNA methylation, consisting of adding a methyl group to DNA, is the most studied mechanism in stroke. This summary reviews studies on how these epigenetic mechanisms play a role in stroke by examining human research. Understanding these mechanisms helps in finding better ways to treat or prevent stroke. Stroke is a major contributor to global mortality and prolonged impairment; it results from complex interactions among genetics, epigenetics and the environment. Epigenetic mechanisms include DNA methylation, histone modification, chromatin restructuring and RNA-dependent processes. These are dynamic and reversible and influence disease risk and progression. Changes in DNA methylation impact stroke risk and outcomes. Genes involved in homocysteine metabolism (AHCY, CBS, MTHFR) show altered methylation in ischemic strokes. Histone modifications, such as acetylation and citrullination, affect gene expression and chromatin structure. Elevated citrullinated histone H3 and altered acetylation patterns are linked to stroke severity and prognosis. Proteins that rearrange chromatin regulate gene expression by altering nucleosome positioning. Although studies in animal models indicate a role for chromatin remodeling in stroke, human studies are needed to confirm these findings. Non-coding RNAs (miRNAs, lncRNAs) play crucial roles in epigenetic regulation and gene expression. miR-124 and lncRNAs (H19, MIAT, MALAT1) are associated with stroke likelihood, severity and recovery. Potential therapies targeting DNA methylation, histone modifications and non-coding RNAs show promise in experimental models. Current stroke treatments, such as tPA and antiplatelet agents, also influence epigenetic modifications, highlighting the potential for integrated therapeutic approaches. Advances in technology and comprehensive omics approaches will enhance understanding of stroke epigenetic changes. Personalized epigenetic therapies may revolutionize stroke management.