Epigenetic modifications as therapeutic targets in atherosclerosis: a focus on DNA methylation and non-coding RNAs
1School of Cardiovascular and Metabolic Medicine & Sciences, King's College London British Heart Foundation Centre of Excellence, London, United Kingdom.
Insights
Cardiovascular disease (CVD) remains a global health threat. Epigenetic changes, like DNA methylation and microRNAs (miRNAs), are increasingly recognized as key factors in atherosclerosis development and potential therapeutic targets.
Area of Science:
- Cardiovascular Medicine
- Molecular Biology
- Genetics
Background:
- Cardiovascular disease (CVD) is a leading cause of global mortality, with atherosclerosis as its primary underlying pathology.
- While genetic factors are known risk factors, environmentally acquired epigenetic changes are increasingly implicated in atherosclerosis development.
- Aberrant DNA methylation and microRNA (miRNA) dysregulation are key epigenetic modifications associated with atherosclerosis.
Purpose of the Study:
- To explore the role of aberrant DNA methylation and miRNA expression in the etiology and progression of atherosclerosis.
- To discuss the potential of these epigenetic changes as biomarkers for disease prediction.
- To evaluate novel cell-based therapeutic strategies targeting epigenetic modifications for reversing atherosclerosis progression.
Main Methods:
- Review of current literature on genetic and epigenetic factors in atherosclerosis.
- Analysis of Genome Wide Association Studies (GWAS) findings related to atherosclerotic vascular disease (AVD).
- Examination of evidence linking DNA methylation and miRNA dysregulation to AVD pathogenesis.
Main Results:
- Genome Wide Association Studies (GWAS) have improved the identification of individuals at genetic risk for atherosclerotic vascular disease (AVD).
- Epigenetic changes, particularly DNA methylation and altered miRNA expression, are increasingly recognized as significant contributors to atherosclerosis.
- The reversible nature of these epigenetic changes presents opportunities for developing novel biomarkers and therapeutic interventions.
Conclusions:
- Epigenetic modifications, including DNA methylation and miRNA dysregulation, are critically involved in the development and progression of atherosclerosis.
- These epigenetic factors hold promise as predictive biomarkers for cardiovascular disease.
- Targeting epigenetic alterations offers a potential therapeutic avenue for reversing atherosclerosis and improving patient outcomes.
Abstract:
Significant progress in the diagnosis and treatment of cardiovascular disease (CVD) has been made in the past decade, yet it remains a leading cause of morbidity and mortality globally, claiming an estimated 17.9 million deaths per year. Although encompassing any condition that affects the circulatory system, including thrombotic blockage, stenosis, aneurysms, blood clots and arteriosclerosis (general hardening of the arteries), the most prevalent underlying hallmark of CVD is atherosclerosis; the plaque-associated arterial thickening. Further, distinct CVD conditions have overlapping dysregulated molecular and cellular characteristics which underlie their development and progression, suggesting some common aetiology. The identification of heritable genetic mutations associated with the development of atherosclerotic vascular disease (AVD), in particular resulting from Genome Wide Association Studies (GWAS) studies has significantly improved the ability to identify individuals at risk. However, it is increasingly recognised that environmentally-acquired, epigenetic changes are key factors associated with atherosclerosis development. Increasing evidence suggests that these epigenetic changes, most notably DNA methylation and the misexpression of non-coding, microRNAs (miRNAs) are potentially both predictive and causal in AVD development. This, together with their reversible nature, makes them both useful biomarkers for disease and attractive therapeutic targets potentially to reverse AVD progression. We consider here the association of aberrant DNA methylation and dysregulated miRNA expression with the aetiology and progression of atherosclerosis, and the potential development of novel cell-based strategies to target these epigenetic changes therapeutically.
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