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Targeting epigenetics and non-coding RNAs in atherosclerosis: from mechanisms to therapeutics
- Source :
- Pharmacology & Therapeutics. 196:15-43
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- Atherosclerosis, the principal cause of cardiovascular death worldwide, is a pathological disease characterized by fibro-proliferation, chronic inflammation, lipid accumulation, and immune disorder in the vessel wall. As the atheromatous plaques develop into advanced stage, the vulnerable plaques are prone to rupture, which causes acute cardiovascular events, including ischemic stroke and myocardial infarction. Emerging evidence has suggested that atherosclerosis is also an epigenetic disease with the interplay of multiple epigenetic mechanisms. The epigenetic basis of atherosclerosis has transformed our knowledge of epigenetics from an important biological phenomenon to a burgeoning field of cardiovascular research. Here, we provide a systematic and up-to-date overview of the current knowledge of three distinct but interrelated epigenetic processes (including DNA methylation, histone methylation/acetylation, and non-coding RNAs), in atherosclerotic plaque development and instability. Mechanistic and conceptual advances in understanding the biological roles of various epigenetic modifiers in regulating gene expression and functions of endothelial cells (vascular homeostasis, leukocyte adhesion, endothelial-mesenchymal transition, angiogenesis, and mechanotransduction), smooth muscle cells (proliferation, migration, inflammation, hypertrophy, and phenotypic switch), and macrophages (differentiation, inflammation, foam cell formation, and polarization) are discussed. The inherently dynamic nature and reversibility of epigenetic regulation, enables the possibility of epigenetic therapy by targeting epigenetic “writers”, “readers”, and “erasers”. Several Food Drug Administration-approved small-molecule epigenetic drugs show promise in pre-clinical studies for the treatment of atherosclerosis. Finally, we discuss potential therapeutic implications and challenges for future research involving cardiovascular epigenetics, with an aim to provide a translational perspective for identifying novel biomarkers of atherosclerosis, and transforming precision cardiovascular research and disease therapy in modern era of epigenetics.
- Subjects :
- 0301 basic medicine
RNA, Untranslated
Angiogenesis
Inflammation
Article
Epigenesis, Genetic
03 medical and health sciences
0302 clinical medicine
Risk Factors
Histone methylation
medicine
Animals
Humans
Pharmacology (medical)
Epigenetics
Foam cell
Pharmacology
biology
business.industry
Immunity
Atherosclerosis
030104 developmental biology
Histone
030220 oncology & carcinogenesis
DNA methylation
biology.protein
medicine.symptom
business
Neuroscience
Epigenetic therapy
Subjects
Details
- ISSN :
- 01637258
- Volume :
- 196
- Database :
- OpenAIRE
- Journal :
- Pharmacology & Therapeutics
- Accession number :
- edsair.doi.dedup.....078fe55604393ff4f0aec9523e37eda8