Epigenetic Mechanisms Affecting the Development of Atherosclerosis: A Narrative Review

Document Type : Narrative Review

Authors

Department of Biotechnology, Institute of Science and High Technology and Environmental Sciences, Graduate University of Advanced Technology, Kerman, Iran

10.22038/jctm.2025.85089.1481

Abstract

Abstract

Introduction: Atherosclerosis is a chronic inflammatory arterial disease that underlies several cardiovascular conditions, including coronary artery disease, heart failure, and stroke. A hallmark of atherosclerosis is the accumulation of fatty plaques, involving various cell types and molecular pathways. The development of this disease involves complex interactions between genetic and environmental factors.

Materials and Methods: A review was conducted using bibliographic databases such as PubMed and Scopus to examine articles on epigenetic alterations and their impact on atherosclerosis and cardiovascular disease. Furthermore, in silico data analyses related to epigenetics and atherosclerosis were also performed.

Results: Epigenetic processes, including DNA methylation, histone modifications, and non-coding RNA, are dynamic modifications that play a crucial role in various stages of atherosclerotic plaque progression. Transgenerational transmission of epigenetic modifications increases cardiovascular disease risk, even in offspring. Inflammation within blood vessel walls is linked to lipid metabolism and is crucial for atherosclerosis development. Macrophages and monocytes, when exposed to inflammatory stimuli, undergo alterations in their genetic and epigenetic profiles, thereby contributing to atherosclerosis progression. Our in silico analysis identified HDAC1, HDAC9, HDAC3, SIRT1, and HDAC6 as key hub genes within a protein-protein interaction network of atherosclerosis-related genes.

Conclusion: Understanding epigenetic regulation can provide insights into gene activation related to functions such as inflammation, lipid metabolism, and vascular remodeling, thus influencing atherosclerosis progression. Considering both genetic and epigenetic mechanisms can provide insight into the molecular processes driving atherosclerosis and inform the development of new therapeutic strategies.

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