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Epigenetic Changes in Diabetes and Cardiovascular Risk
Open accessAbstract
Cardiovascular complications remain the leading causes of morbidity and premature mortality in patients with diabetes mellitus. Studies in humans and preclinical models demonstrate lasting gene expression changes in the vasculopathies initiated by previous exposure to high glucose concentrations and the associated overproduction of reactive oxygen species. The molecular signatures of chromatin architectures that sensitize the genome to these and other cardiometabolic risk factors of the diabetic milieu are increasingly implicated in the biological memory underlying cardiovascular complications and now widely considered as promising therapeutic targets. Atherosclerosis is a complex heterocellular disease where the contributing cell types possess distinct epigenomes shaping diverse gene expression. Although the extent that pathological chromatin changes can be manipulated in human cardiovascular disease remains to be established, the clinical applicability of epigenetic interventions will be greatly advanced by a deeper understanding of the cell type–specific roles played by writers, erasers, and readers of chromatin modifications in the diabetic vasculature. This review details a current perspective of epigenetic mechanisms of macrovascular disease in diabetes mellitus and highlights recent key descriptions of chromatinized changes associated with persistent gene expression in endothelial, smooth muscle, and circulating immune cells relevant to atherosclerosis. Furthermore, we discuss the challenges associated with pharmacological targeting of epigenetic networks to correct abnormal or deregulated gene expression as a strategy to alleviate the clinical burden of diabetic cardiovascular disease.
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“A diurnal, well‐accepted and extensively studied model for T2DM 48, 51, 100, 101, 102, 103 is the sand rat, (Psammomys obesus).”
From The Circadian Syndrome: is the Metabolic Syndrome and much more! (2019) · cites this paper as [48]
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Metadata
- Authors
- Keating, S. T., Plutzky, J., & El-Osta, A.
- Affiliations
- Brigham and Women's Hospital (US)
- From the Epigenetics in Human Health and Disease Laboratory (S.T.K., A.E.-O.) and Epigenomics Profiling Facility (A.E.-O.), Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria, Australia; Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA (J.P.); Department of Pathology, The University of Melbourne, Victoria, Australia (A.E.-O.); and Central Clinical School, Department of Medicine, Monash...
- Venue
- Circulation Research
- Published
- 2016-05-27
- Volume
- 118
- Issue
- 11
- Pages
- 1706-1722
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- PMC
- PMC5593074
- OpenAlex
- W2401080925
- Cited by
- 139
- References
- 205
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 17 · 2023: 9 · 2022: 12 · 2021: 13 · 2020: 16 · 2019: 14 · 2018: 19 · 2017: 16 · 2016: 4
- FWCI
- 9.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- Funders
- State Government of Victoria
- National Institutes of Health
- Medical Research Council
- National Health and Medical Research Council
- National Heart, Lung, and Blood Institute (R56HL125894, P01HL048743)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- epigenetics, diabetes mellitus, cardiovascular disease, atherosclerosis, diabetic vascular complications, chromatin modification, endothelial cells, vascular smooth muscle cells, immune cells, high glucose, reactive oxygen species, epigenetic drug targets, gene expression regulation
- MeSH terms
- Animals, Diabetes Mellitus, Diabetic Angiopathies, Humans, Chromatin Assembly and Disassembly, Epigenesis, Genetic
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