Inflammation marks all stages of atherogenesis. DNA hypermethylation in the whole genome or specific genes is associated with @entity32 and @entity65 . Therefore, we aimed to study whether inhibiting DNA methylation by DNA methyltransferase inhibitor @entity11508 (5-aza-dC) ameliorates @entity731 in @entity1748 knockout (Ldlr(-/-)) @entity19 . Ldlr(-/-) @entity19 were fed an atherogenic diet and adminisered saline or 5-aza-dC (0.25 mg/kg) for up to 30 weeks. 5-aza-dC treatment markedly decreased @entity731 development in Ldlr(-/-) @entity19 without changes in body weight, plasma lipid profile, macrophage @entity165 levels and plaque lipid content. Instead, this effect was associated with decreased macrophage @entity32 . Macrophages with 5-aza-dC treatment had downregulated expression of genes involved in @entity32 ( @entity637 , @entity777 , @entity635 , and inducible nitric oxidase) and chemotaxis (CD62/L-selectin, chemokine [C-C motif] ligand 2/ @entity1750 [ @entity1750 / @entity1750 ], @entity638 , @entity27505 , and @entity1750 receptor @entity13766 ). This resulted in attenuated macrophage migration and adhesion to endothelial cells and reduced macrophage infiltration into atherosclerotic plaques. 5-aza-dC also suppressed macrophage endoplasmic reticulum stress, a key upstream signal that activates macrophage @entity32 and apoptotic pathways. Finally, 5-aza-dC demethylated liver X receptor a (LXRa) and peroxisome proliferator-activated receptor y1 (PPARy1) promoters, which are both enriched with CpG sites. This led to overexpression of LXRa and PPARy, which may be responsible for 5-aza-dC's anti-inflammatory and atheroprotective effect. Our findings provide strong evidence that DNA methylation may play a significant role in @entity65 and serve as a therapeutic target for prevention and treatment of @entity731 .

Inhibiting DNA Methylation by XXXX Ameliorates Atherosclerosis Through Suppressing Macrophage Inflammation.

@entity32 :: ('MESH:D007249', 'Disease') :: ['inflammation'] @entity1748 :: ('16835(Tax:10090)', 'Gene') :: ['low-density lipoprotein receptor'] @entity27505 :: ('20308(Tax:10090)', 'Gene') :: ['CCL9'] @entity1750 :: ('20296(Tax:10090)', 'Gene') :: ['CCL2', 'MCP-1'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity635 :: ('16176(Tax:10090)', 'Gene') :: ['IL-1b'] @entity13766 :: ('12772(Tax:10090)', 'Gene') :: ['CCR2'] @entity638 :: ('20304(Tax:10090)', 'Gene') :: ['CCL5'] @entity777 :: ('16193(Tax:10090)', 'Gene') :: ['IL-6'] @entity731 :: ('MESH:D050197', 'Disease') :: ['atherosclerosis'] @entity637 :: ('21926(Tax:10090)', 'Gene') :: ['TNF-a'] @entity65 :: ('MESH:D002318', 'Disease') :: ['cardiovascular diseases'] @entity165 :: ('MESH:D002784', 'Chemical') :: ['cholesterol'] @entity11508 :: ('MESH:C014347', 'Chemical') :: ["5-aza-2'-deoxycytidine"]
@entity11508 :: (MESH:C014347,Chemical) :: ['5-Aza-2'-deoxycytidine']
