Epigenetic Changes in Endothelial Progenitors as a Possible Cellular Basis for Glycemic Memory in Diabetic Vascular Complications

Table 2

Summary of in vitro and in vivo studies showing epigenetic marks associated with diabetic vascular complications. Studies directly related to the endothelial glycemic memory.

Type of epigenetic change	Location	Enzyme	Cell type	Target genes/functions	Reference
HAc and HMe	↑ H3K9Ac, ↑ H3K4me3		T1D monocytes	↑ STAT1, ↑ TNF, and ↑ IL1A	[76]
HAc and HMe	↑ H3K9Ac, ↑ H3K12Ac, ↑ H3K4me2, and; ↑ H3K4me3		HUVECs	↑ eNOS	[89]
HMe	↑ H3K27me3		eEPCs	↑ eNOS	[90]
HMe	↑ H3K4me1, ↓ H3K9me2, and ↓ H3K9me3	Set7, SUV39h1, and LSD-1	HG HMECs	↑ NFB P65	[80]
HMe	↑ H3K4me1	Set7	HG HMECs	↑ ICAM1, ↑ IL8, and ↓ HMOX1	[81]
HMe	↓ H3K4me1, ↓ H3K4me2	LSD-1	HG rat retinal ECs	↓ Sod2	[77]
HAc	↓ H3 acetylation	↓ HAT ↑ HDAC1, HDAC2, and HDAC8	HG rat retinal ECs		[79]
HAc	↑ H3 acetylation	HAT cofactor p300	HG HUVECs	↑ ET-1, ↑ FN, ↑ VEGF, ↑ NFB, ↑ AP-1,; ↑ MEF2, and ↑ GATA	[83]
HMe	↑ H3K4me	Set7/9	Monocytes	↑ NFB, ↑ TNF, ↑ RAGE, and ↑ JMJD3; ↑ monocyte adhesion to ECs	[82]
DNAme	↑ Promoter of UNC13B		T1D whole blood cells	↓ UNC13B; ↑ chronic kidney disease	[91]
DNAme	↑ Promoter of POLG1		HG rat retinal Ecs	↓ POLG1; ↑ glomerular apoptosis, ↑ d-loop damage in mt DNA	[93]
DNAme	↑ Global hypomethylation		Diabetic foot ulcer fibroblasts	↓ Wound healing process	[92]

HAc, histone acetylation; HMe, histone methylation; DNAme, DNA methylation; HG, hyperglycemic.