Epigenetic Mechanisms Linking Atherosclerosis to Ischemic Stroke: Insights from DNA Methylation and Transcriptome Integration

Binrong Ding¹Yiqun Wang²Junfeng Li¹Xuewei Zhang^3,4,5*Zhengqing Wan^6,7*Hao Wang^1*

• ¹People's Hospital of Ningxiang City, Hunan University of Chinese Medicine, Changsha, China
• ²Department of Geriatrics, The Third Xiangya Hospital of Central South University, Changsha, China
• ³Health Management Center, Xiangya Hospital, Central South University, Hunan, Hunan Province, China
• ⁴National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
• ⁵Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Anhui Province, China
• ⁶Department of Medical Genetics, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, China
• ⁷MOE Key Lab of Rare Pediatric Diseases, School of Life Sciences, University of South China, Changsha, China

Background: Ischemic stroke (IS) is a major cause of mortality and disability, with atherosclerosis (AS) as a primary risk factor. DNA methylation plays a critical role in AS development, but its regulatory mechanisms remain unclear. This study aims to investigate the epigenetic regulatory mechanisms linking AS and IS by integrating DNA methylation and transcriptome data from public databases.Methods: This study integrated DNA methylation (GSE46394) and transcriptome data (GSE111782 and GSE162955) from public databases to investigate the molecular mechanisms linking AS and IS.Differentially methylated CpG positions (DMPs) and differentially expressed genes (DEGs) were identified (p < 0.05). Subsequent gene annotation and enrichment analyses were performed to uncover potential molecular mechanisms underlying the relationship between AS and IS.Results: A total of 5,396 consistent DMPs were identified in aortic and carotid atherosclerotic lesions, with enriched pathways such as MAPK signaling and Hippo signaling. Transcriptome analysis revealed 1,147 DEGs in AS plaques and 1,321 DEGs in IS brain tissues, enriched in pathways including neuroactive ligand-receptor interactions, calcium signaling, and vascular smooth muscle contraction. Overlapping analyses identified shared processes like actin filament polymerization, cell migration, and MAPK cascade regulation, as well as pathways such as adrenergic signaling, and apelin signaling.This study highlights the pivotal role of epigenetic regulation in AS and IS, uncovering key pathways and molecular processes involved in their progression. Future studies should validate these findings in larger cohorts and integrate multi-omics approaches for a comprehensive understanding.