title: Elevated plasma prostaglandins and acetylated histone in monocytes in Type 1 diabetes patients.
abstract: OBJECTIVE
  Inflammation is implicated in diabetes and cyclooxygenase (COX) is involved in vascular inflammatory processes, participating in both atherosclerosis and thrombosis. The aims were to determine whether levels of monocyte COX and plasma COX metabolites are increased in Type 1 diabetic patients and to determine whether these could be linked to histone hyperacetylation.
  
  
  METHODS
  Monocytes from 19 Type 1 diabetic and 39 non-diabetic control subjects were probed for COX and acetylated histone H4 proteins by immunoblotting. Plasma COX metabolite levels [thromboxane B(2) (TXB(2)) and prostaglandin E(2) (PGE(2))] were determined by enzyme immunoassay.
  
  
  RESULTS
  Monocyte COX-2 expression was significantly up-regulated (1.3-fold) in diabetic relative to the non-diabetic control subjects and plasma PGE(2) was markedly elevated (2.7-fold). In diabetic subjects, monocyte acetylated histone H4 levels were significantly elevated; sub-group analysis indicated that the increased histone acetylation was found only in the complication-free group.
  
  
  CONCLUSIONS
  Results support increased inflammatory activity in Type 1 diabetes that involves COX-2 and increased prostaglandin production, which may predispose patients to cardiovascular events. The observation of elevated histone acetylation only in complication-free diabetic subjects suggests that this may be a protective mechanism. This merits further investigation as histone hyperacetylation has been associated with reduced expression of factors involved in vascular injury and remodelling.
authors.affiliation: School of Medical Sciences, RMIT University, Vic., Australia.
authors.forename: S S H
authors.initials: SS
authors.lastname: Chen
authors.forename: A J
authors.initials: AJ
authors.lastname: Jenkins
authors.forename: H
authors.initials: H
authors.lastname: Majewski
mesh_terms: D000107:Acetylation; D000328:Adult; D001315:Australia; D003430:Cross-Sectional Studies; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D005260:Female; D006657:Histones / Q000096:biosynthesis; D006801:Humans; D008297:Male; D009000:Monocytes / Q000201:enzymology*; D010949:Plasma / Q000201:enzymology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011458:Prostaglandins E / Q000096:biosynthesis; D013929:Thromboxane B2 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D006657:Histones; D011458:Prostaglandins E; D013929:Thromboxane B2; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases