Epigenetic perspective on atherosclerotic cardiovascular diseases: The holistic principle of systems biology and epigenetic reasoning

Atherosclerosis and coronary artery disease are the main causes of impairment and cardiac death, placing a significant burden on our health-care system. This review focuses on elucidating the involvement of various epigenetic mechanisms in the genesis and progression of cardiovascular diseases (CVDs), particularly chronic CVDs. The deregulation of epigenetic mechanisms plays a crucial role in the progression of CVDs, prompting exploration into novel preventive approaches. Advancements in molecular procedures, network-based approaches, and data analysis have identified new targets in CVDs, permitting the utilization of individualized epigenetic factors for personalized diagnosis and treatment. While promising for improving diagnostic and prognostic assessments, the clinical implementation of epigenetic biomarkers lags behind. Multicenter clinical documentation in a large sample population is crucial to confidently ascertain the clinical utility of specific epigenetic biomarkers. Of particular interest is the interplay between epigenetics and the conflict between the gene-based reductionist theory and the holistic principle of systems biology (SB). The holistic principle analyzes the structural organization and regulation of biological networks, influencing the genesis and progression of complex cardiac diseases like CVDs. This review emphasizes the complexity of CVDs, elucidates the interrelationship between disease networks and epigenetic mechanisms, and highlights the importance of the holistic principle of SB, coupled with artificial intelligence, in clarifying this interrelationship. The constant and uninterrupted epigenetic impact holds immense potential for advancing our understanding of disease progression and treatment across cells and tissues. Despite these advancements, the full integration of the epigenetic impact into medical practice remains incomplete, with limited utilization in clinical applications. Nevertheless, it is likely that in the near future, the epigenetic regulation of gene expression, with its lifelong and extended effects on health, will become an integral part of everyday clinical practice.