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Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.
Nitro-fatty acids in cardiovascular regulation and diseases: characteristics and molecular mechanisms
1 Cardiovascular Center, Department of Internal Medicine, University of Michigan, North Campus Research Complex 26, 2800 Plymouth Road, Ann Arbor, MI 48109, USA
2 Department of Pharmacology and Chemical Biology, University of Pittsburgh, E1343 Thomas E. Starzl Biomedical Science Tower, 200 Lothrop Street, Pittsburgh, PA 15213, USA
Abstract
Electrophilic nitro-fatty acids (NO2-FAs) are endogenously formed by redox reactions of nitric oxide (•NO)-and nitrite (•NO2)-derived nitrogen dioxide with unsaturated fatty acids. Nitration preferentially occurs on polyunsaturated fatty acids with conjugated dienes under physiological or pathophysiological conditions such as during digestion, metabolism and as adaptive inflammatory processes. Nitro-fatty acids are present in free and esterified forms achieving broad biodistribution in humans and experimental models. Structural, functional and biological characterization of NO2-FAs has revealed clinically relevant protection from inflammatory injury in a number of cardiovascular, renal and metabolic experimental models. NO2-FAs are engaged in posttranslational modifications (PTMs) of a selective redox sensitive pool of proteins and regulate key adaptive signaling pathways involved in cellular homeostasis and inflammatory response. Here, we review and update the biosynthesis, metabolism and signaling actions of NO2-FAs, highlighting their diverse protective roles relevant to the cardiovascular system.
Keywords
- Nitro-fatty acids
- Cardiovascular Diseases
- Nitrite
- Nitrate
- Therapeutics
- Inflammation
- Metabolism
- Review
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