Year: 2016
Type: article
Abstract: The objective of the present study was to assess the effect of elevating epoxygenated fatty acids on retinal vascular inflammation. To stimulate inflammation we utilized TNFα, a potent pro-inflammatory mediator that is elevated in the serum and vitreous of diabetic patients. In TNFα-stimulated primary human retinal microvascular endothelial cells, total levels of epoxyeicosatrienoic acids (EETs), but not epoxydocosapentaenoic acids (EDPs), were significantly decreased. Exogenous addition of 11,12-EET or 19,20-EDP when combined with 12-(3-adamantane-1-yl-ureido)-dodecanoic acid (AUDA), an inhibitor of epoxide hydrolysis, inhibited VCAM-1 and ICAM-1 expression and protein levels; conversely the diol product of 19,20-EDP hydrolysis, 19,20-DHDP, induced VCAM1 and ICAM1 expression. 11,12-EET and 19,20-EDP also inhibited leukocyte adherence to human retinal microvascular endothelial cell monolayers and leukostasis in an acute mouse model of retinal inflammation. Our results indicate that this inhibition may be mediated through an indirect effect on NFκB activation. This is the first study demonstrating a direct comparison of EET and EDP on vascular inflammatory endpoints, and we have confirmed a comparable efficacy from each isomer, suggesting a similar mechanism of action. Taken together, these data establish that epoxygenated fatty acid elevation will inhibit early pathology related to TNFα-induced inflammation in retinal vascular diseases.
Source: Scientific Reports
DOI: 10.1038/srep39211
Institutions: Vanderbilt University, Vanderbilt University Medical Center
Language: English
Subfield: Biochemistry
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,690
Funders: Christopher and Dana Reeve Foundation, Research to Prevent Blindness, Vanderbilt University, National Institutes of Health, National Eye Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Advancing Translational Sciences
Awards: G1182793083, G1344704808, G1690227563, G1805704937, G1806196891, G2019238319, G3814674971, G4425699080, Initiative for Maximizing Student Development, Molecular Mechanisms of Retinal Vascular Disease, The Vanderbilt Institute for Clinical and Translational Research (VICTR), G9000012206, G9000033427, G9000043240, G9000052735, G9000088904, G9000330368, Training Grant in Vision Research
OpenAlex ID: W2562397748