Incretin drugs effect on epigenetic machinery: New potential therapeutic implications in preventing vascular diabetic complications.
Atherosclerosis
/ genetics
Blood Glucose
/ drug effects
Body Mass Index
Carotid Intima-Media Thickness
Cell Line
DNA Methylation
/ drug effects
Diabetes Complications
/ genetics
Diabetes Mellitus, Type 2
/ complications
Endothelial Cells
/ drug effects
Epigenesis, Genetic
/ drug effects
Gene Expression
/ drug effects
Glucagon-Like Peptide-1 Receptor
/ genetics
Glucose
/ genetics
Humans
Incretins
/ pharmacology
NF-kappa B
/ genetics
Superoxide Dismutase
/ genetics
DNA methylation
atherosclerosis progression
incretin based drugs
type 2 diabetes
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
14
04
2020
revised:
25
09
2020
accepted:
06
10
2020
pubmed:
23
10
2020
medline:
23
4
2021
entrez:
22
10
2020
Statut:
ppublish
Résumé
The effect of GLP-1R agonists on DNA methylation levels of NF-κB and SOD2 genes in human aortic endothelial cells exposed to high glucose and in diabetic patients treated and not with incretin-based drugs, was evaluated. Methylation levels, mRNA and protein expression of NF-κB and SOD2 genes were measured in human endothelial cells exposed to high glucose for 7 days and treated with GLP-1R agonists. Methylation status of NF-κB and SOD2 promoter was also analyzed in 128 diabetics and 116 nondiabetics and correlated with intima media thickness (ITM), an early marker of atherosclerotic process. Cells exposed to high glucose showed lower NF-κB and SOD2 methylation levels, increased NF-κB and reduced SOD2 expression compared to normal glucose cells. Co-treatment with GLP-1 agonists prevented methylation and genes expression changes induced by high glucose. Both high glucose and incretins exposure increased DNA methyltransferases and demethylases levels. In diabetics, incretin treatment resulted a significant predictor of NF-κB DNA methylation, independently of age, sex, body mass index (BMI), glucose and plasma lipid levels. NF-κB DNA methylation inversely correlated with IMT after adjusting for multiple covariates. Our results firstly provide new evidences of an additional mechanism by which incretin drugs could prevent vascular diabetic complications.
Identifiants
pubmed: 33090591
doi: 10.1096/fj.202000860RR
doi:
Substances chimiques
Blood Glucose
0
Glucagon-Like Peptide-1 Receptor
0
Incretins
0
NF-kappa B
0
Superoxide Dismutase
EC 1.15.1.1
superoxide dismutase 2
EC 1.15.1.1
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
16489-16503Informations de copyright
© 2020 Federation of American Societies for Experimental Biology.
Références
Kaur R, Kaur M, Singh J. Endothelial dysfunction and platelet hyperactivity in type 2 diabetes mellitus: molecular insights and therapeutic strategies. Cardiovasc Diabetol. 2018;17(1):121.
Jin J, Wang X, Zhi X, Meng D. Epigenetic regulation in diabetic vascular complications. J Mol Endocrinol. 2019;63(4):R103-R115. https://doi.org/10.1530/JME-19-0170.
Muka T, Nano J, Voortman T, et al. The role of global and regional DNA methylation and histone modifications in glycemic traits and type 2 diabetes: a systematic review. Nutr Metab Cardiovasc Dis. 2016;26(7):553-566.
Tabaei S, Tabaee SS. DNA methylation abnormalities in atherosclerosis. Artif Cells Nanomed Biotechnol. 2019;47(1):2031-2041.
Yuan EF, Yang Y, Cheng L, et al. Hyperglycaemia affects global 5-methylcytosine and 5-hydroxymethylcytosine in blood genomic DNA through upregulation of SIRT6 and TETs. Clin Epigenetics. 2019;11(1):63.
Chen Z, Li S, Subramaniam S, Shyy JY, Chien S. Epigenetic regulation: a new frontier for biomedical engineers. Annu Rev Biomed Eng. 2017;19:195-219.
Mishra M, Kowluru RA. Epigenetic modification of mitochondrial DNA in the development of diabetic retinopathy. Invest Ophthalmol Vis Sci. 2015;56(9):5133-5142.
Zhang H, Li A, Zhang W, Huang Z, Wang J, Yi B. High glucose-induced cytoplasmic translocation of Dnmt3a contributes to CTGF hypo-methylation in mesangial cells. Biosci Rep. 2016;36(4).e00362
Kowluru RA, Shan Y, Mishra M. Dynamic DNA methylation of matrix metalloproteinase-9 in the development of diabetic retinopathy. Lab Invest. 2016;96(10):1040-1049.
Dhliwayo N, Sarras MP Jr, Luczkowski E, Mason SM, Intine RV. Parp inhibition prevents ten-eleven translocase enzyme activation and hyperglycaemia-induced DNA demethylation. Diabetes. 2014;63(9):3069-3076.
Gallego-Colon E, Wojakowski W, Francuz T. Incretin drugs as modulators of atherosclerosis. Atherosclerosis. 2018;278:29-38.
Jojima T, Uchida K, Akimoto K, et al. Liraglutide, a GLP-1 receptor agonist, inhibits vascular smooth muscle cell proliferation by enhancing AMP-activated protein kinase and cell cycle regulation, and delays atherosclerosis in ApoE deficient mice. Atherosclerosis. 2017;261:44-51.
Sudo M, Li Y, Hiro T, et al. Inhibition of plaque progression and promotion of plaque stability by glucagon-like peptide-1 receptor agonist: serial in vivo findings from iMap-IVUS in Watanabe heritable hyperlipidemic rabbits. Atherosclerosis. 2017;265:283-291.
Barbieri M, Marfella R, Esposito A, et al. Incretin treatment and atherosclerotic plaque stability: role of adiponectin/APPL1 signaling pathway. J Diabetes Complications. 2017;31(2):295-303.
Yasuda H, Mizukami K, Hayashi M, Kamiya T, Hara H, Adachi T. Exendin-4 promotes extracellular-superoxide dismutase expression in A549 cells through DNA demethylation. J Clin Biochem Nutr. 2016;58(1):34-39.
Pinney SE, Jaeckle Santos LJ, Han Y, Stoffers DA, Simmons RA. Exendin-4 increases histone acetylase activity and reverses epigenetic modifications that silence Pdx1 in the intrauterine growth retarded rat. Diabetologia. 2011;54(10):2606-2614.
American Diabetes Association. Classification and diagnosis of diabetes: standards of medical care in diabetes-2020. Diabetes Care. 2020;43(Suppl 1):S98-S110.
Garczorz W, Gallego-Colon E, Kosowska A, et al. Exenatide exhibits anti-inflammatory properties and modulates endothelial response to tumor necrosis factor α-mediated activation. Cardiovasc Ther. 2018;36(2):e12317.
Beckman JA, Creager MA, Libby P. Diabetes and atherosclerosis: epidemiology, pathophysiology, and management. JAMA. 2002;287(19):2570-2581.
Ziyadeh FN, Sharma K. Overview: combating diabetic nephropathy. J Am Soc Nephrol. 2003;14(5):1355-1357.
Fong DS, Aiello L, Gardner TW, et al. Diabetic retinopathy. Diabetes Care. 2003;26(1):226-229.
Natarajan R, Nadler JL. Lipid inflammatory mediators in diabetic vascular disease. Arterioscler Thromb Vasc Biol. 2004;24(9):1542-1548.
Vincent AM, Calabek B, Roberts L, Feldman EL. Biology of diabetic neuropathy. Handb Clin Neurol. 2013;115:591-606.
Forbes JM, Cooper ME. Mechanisms of diabetic complications. Physiol Rev. 2013;93(1):137-188.
Khullar M, Cheema BS, Raut SK. Emerging evidence of epigenetic modifications in vascular complication of diabetes. Front Endocrinol (Lausanne). 2017;29(8):237.
Ling C, Rönn T. Epigenetics in human obesity and type 2 diabetes. Cell Metab. 2019;29(5):1028-1044.
Garber AJ. Long-acting glucagon-like peptide 1 receptor agonists: a review of their efficacy and tolerability. Diabetes Care. 2011;34(Suppl 2):S279-S284.
Sommese L, Zullo A, Mancini FP, Fabbricini R, Soricelli A, Napoli C. Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus. Epigenetics. 2017;12(6):401-415.
Liu T, Zhang L, Joo D, Sun SC. NF-κB signaling in inflammation. Signal Transduct Target Ther. 2017;2:pii: 17023.
He J, Liu X, Su C, et al. Inhibition of mitochondrial oxidative damage improves reendothelialization capacity of endothelial progenitor cells via SIRT3 (Sirtuin 3)-enhanced SOD2 (Superoxide Dismutase 2) deacetylation in hypertension. Arterioscler Thromb Vasc Biol. 2019;39(8):1682-1698. https://doi.org/10.1161/ATVBAHA.119.312613.
Wei H, Prabhu L, Hartley AV, et al. Methylation of NF-κB and its role in gene regulation. 2017. https://doi.org/10.5772/intechopen.72552.
Yasuda H, Ohashi A, Nishida S, et al. Exendin-4 induces extracellular-superoxide dismutase through histone H3 acetylation in human retinal endothelial cells. J Clin Biochem Nutr. 2016;59(3):174-181. https://doi.org/10.3164/jcbn.16-26
El-Osta A, Brasacchio D, Yao D, et al. Transient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemia. J Exp Med. 2008;10:2409-2417. https://doi.org/10.1084/jem.20081188.
Jenkins AJ, Welsh P, Petrie JR. Metformin, lipids and atherosclerosis prevention. Curr Opin Lipidol. 2018;29(4):346-353. https://doi.org/10.1097/MOL.0000000000000532.