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Epigenetic Mechanisms in Diabetic Vascular Complications and Metabolic Memory: The 2020 Edwin Bierman Award Lecture

Macrovascular complications such as atherosclerosis, myocardial infarction and stroke, and microvascular complications such as nephropathy, retinopathy, and neuropathy are the major causes of increased morbidity and mortality in both type 1 and type 2 diabetes. Increased inflammation, oxidative stre...

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Autor principal: Natarajan, Rama
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881871/
https://www.ncbi.nlm.nih.gov/pubmed/33472942
http://dx.doi.org/10.2337/dbi20-0030
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author_facet Natarajan, Rama
author_sort Natarajan, Rama
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description Macrovascular complications such as atherosclerosis, myocardial infarction and stroke, and microvascular complications such as nephropathy, retinopathy, and neuropathy are the major causes of increased morbidity and mortality in both type 1 and type 2 diabetes. Increased inflammation, oxidative stress, and fibrosis are common features in most diabetes complications. Although extensive studies have examined the biochemical pathways leading to the expression of inflammatory, profibrotic, and other pathological genes, as well as genetic factors related to diabetes and associated complications, much less is known about the contribution of epigenetic changes that occur without alterations in the DNA sequence. Environmental factors, lifestyles, and improper diet implicated in diabetes can affect epigenetic states. Epigenetic modifications, including DNA methylation and histone modifications, can alter gene transcription in response to environmental stimuli and cooperate with noncoding RNAs. These epigenetic modifications have been observed in various target cells under diabetic conditions. Moreover, epigenetics has also been implicated in the phenomenon of metabolic memory observed in clinic trials and animal studies, in which prior episodes of poor glycemic control can confer continued risk of complications despite subsequent glucose normalization. Epigenome-wide association studies in cohorts with diabetes are uncovering epigenotype variations that provide new insights into diabetic vascular complications. Here, I discuss the role of epigenetics and noncoding RNAs in diabetes complications and metabolic memory, and their translation potential to serve as biomarkers and drug targets to improve clinical management of diabetic vascular complications.
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spelling pubmed-78818712022-02-01 Epigenetic Mechanisms in Diabetic Vascular Complications and Metabolic Memory: The 2020 Edwin Bierman Award Lecture Natarajan, Rama Diabetes ADA Award Lectures Macrovascular complications such as atherosclerosis, myocardial infarction and stroke, and microvascular complications such as nephropathy, retinopathy, and neuropathy are the major causes of increased morbidity and mortality in both type 1 and type 2 diabetes. Increased inflammation, oxidative stress, and fibrosis are common features in most diabetes complications. Although extensive studies have examined the biochemical pathways leading to the expression of inflammatory, profibrotic, and other pathological genes, as well as genetic factors related to diabetes and associated complications, much less is known about the contribution of epigenetic changes that occur without alterations in the DNA sequence. Environmental factors, lifestyles, and improper diet implicated in diabetes can affect epigenetic states. Epigenetic modifications, including DNA methylation and histone modifications, can alter gene transcription in response to environmental stimuli and cooperate with noncoding RNAs. These epigenetic modifications have been observed in various target cells under diabetic conditions. Moreover, epigenetics has also been implicated in the phenomenon of metabolic memory observed in clinic trials and animal studies, in which prior episodes of poor glycemic control can confer continued risk of complications despite subsequent glucose normalization. Epigenome-wide association studies in cohorts with diabetes are uncovering epigenotype variations that provide new insights into diabetic vascular complications. Here, I discuss the role of epigenetics and noncoding RNAs in diabetes complications and metabolic memory, and their translation potential to serve as biomarkers and drug targets to improve clinical management of diabetic vascular complications. American Diabetes Association 2021-02 2021-01-14 /pmc/articles/PMC7881871/ /pubmed/33472942 http://dx.doi.org/10.2337/dbi20-0030 Text en © 2021 by the American Diabetes Association https://www.diabetesjournals.org/content/licenseReaders may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www.diabetesjournals.org/content/license.
spellingShingle ADA Award Lectures
Natarajan, Rama
Epigenetic Mechanisms in Diabetic Vascular Complications and Metabolic Memory: The 2020 Edwin Bierman Award Lecture
title Epigenetic Mechanisms in Diabetic Vascular Complications and Metabolic Memory: The 2020 Edwin Bierman Award Lecture
title_full Epigenetic Mechanisms in Diabetic Vascular Complications and Metabolic Memory: The 2020 Edwin Bierman Award Lecture
title_fullStr Epigenetic Mechanisms in Diabetic Vascular Complications and Metabolic Memory: The 2020 Edwin Bierman Award Lecture
title_full_unstemmed Epigenetic Mechanisms in Diabetic Vascular Complications and Metabolic Memory: The 2020 Edwin Bierman Award Lecture
title_short Epigenetic Mechanisms in Diabetic Vascular Complications and Metabolic Memory: The 2020 Edwin Bierman Award Lecture
title_sort epigenetic mechanisms in diabetic vascular complications and metabolic memory: the 2020 edwin bierman award lecture
topic ADA Award Lectures
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881871/
https://www.ncbi.nlm.nih.gov/pubmed/33472942
http://dx.doi.org/10.2337/dbi20-0030
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