208 - Protective Role of Nitro-oleic Acid in Development of Vascular Dysfunction

Abstract

It is becoming increasingly evidence that nitration products of unsaturated fatty acids represent an important class of endogenous biological mediators, generated as an adaptive response of organism to oxidative and nitrative stress. The purpose of our study was to define the role of nitro-oleic acid (NO 2 -OA) in prevention and treatment of vascular dysfunction in different models (atrial fibrosis and pulmonary hypertension). The effect of NO 2 -OA was tested in different cell types (including macrophages, neutrophils, fibroblasts, endothelial, and smooth muscle cells) both in vivo and in vitro . Our results showed that NO 2 -OA significantly improves the heart functions and overall outcome of animals with atrial fibrosis and pulmonary hypertension. These effects were associated with reduced polarization of macrophages toward pro-inflammatory and immuno-regulatory subsets, decreased activation of different signaling pathways as well as production of pro-inflammatory and pro-fibrotic mediators. NO 2 -OA prevents pathological activation of endothelial cells characterized by reduced production of pro-inflammatory cytokines and chemokines, expression of adhesive molecules as well as their transformation to the pro-fibrotic phenotype. In aggregate, our study provides unique results showing the protective effects of NO 2 -OA in progression of vascular inflammation.