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Soluble epoxide hydrolase contributes to the endothelial dysfunction of peripheral conduit arteries in type 2 diabetic patients
Author(s) -
Duflot Thomas,
RemyJouet Isabelle,
Morisseau Christophe,
Wils Julien,
Li Dongyang,
Prevost Gaetan,
Joannides Robinson,
Bellien Jeremy
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.561.9
Subject(s) - epoxide hydrolase 2 , endothelial dysfunction , vasodilation , medicine , reactive oxygen species , endothelium , endocrinology , diabetes mellitus , peripheral blood mononuclear cell , artery , type 2 diabetes , type 1 diabetes , brachial artery , chemistry , blood pressure , biochemistry , enzyme , in vitro
This study addressed the hypothesis that soluble epoxide hydrolase (sEH), which metabolizes the vasodilator and anti‐inflammatory epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids (DHETs), contributes to conduit artery endothelial dysfunction in type 2 diabetic patients. We measured radial artery endothelium‐dependent flow‐mediated dilatation in 29 patients with well‐controlled type 2 diabetes (HbA1c=6.7±0.6%) and 37 control subjects in response to hand skin heating. We quantified the local plasma concentrations of EETs, DHETs, the NO metabolite nitrite and reactive oxygen species (ROS) at baseline and during heating. The sEH protein expression and activity were measured in peripheral blood mononuclear cells (PBMCs) isolated from patients and controls. Flow‐mediated dilatation was reduced in diabetic patients compared to controls, without change in flow variation and endothelium‐independent dilatation to glyceryl trinitrate. Diabetic patients displayed an elevation in ROS levels and a complete loss of NO release and in EETs production, assessed by the sum of total EETs and DHETs, during the flow stimulation. The conversion of EETs to DHETs (DHET‐to‐EET ratio) was enhanced at baseline and further increased during heating in diabetic patients compared to controls. Moreover, sEH expression and activity were increased in diabetic PBMCs. This study demonstrates that an increased degradation of EETs by sEH contributes with altered NO bioavailability to conduit artery endothelial dysfunction in type 2 diabetic patients. Inhibitors of sEH may be useful to improve endothelial function and thus cardiovascular prognosis in these patients. Support or Funding Information This study was funded by a grant from the Fondation de France (2011‐20459) and supported by National Institute of Environmental Health Sciences grant R01‐ES002710. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .