ARS | Publication request: Impact of circulating esterified eicosanoids and other oxylipins on endothelial function

Submitted to: Current Atherosclerosis Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: August 1, 2009
Publication Date: November 11, 2009
Citation: Shearer, G., Newman, J.W. 2009. Impact of circulating esterified eicosanoids and other oxylipins on endothelial function. Current Atherosclerosis Reports. Vol. 11:403-410.

Interpretive Summary: The oygenation of lipids produces an array of important mediators of inflammation and vascular health, the oxylipins, with emerging roles in atherosclerosis development and progression. These lipids are commonly thought to act in or near cells/tissues where they are produced. However, many of these lipids are found chemically incorporated into membranes and bulk lipid pools (including triglyceride) as esters in both cells and circulating lipoprotein particles. This review focuses on recent work identifying esterified oxylipins in circulation, primarily within lipoproteins, and their effects on endothelial function. These esterified mediators, when released by lipases, can increase endothelial inflammation markers consistent with known roles of lipoproteins in endothelial dysfunctions. Challenges to our understanding of this oxylipin compartment including the need to consider the non-arachidonate-derived oxylipins and the implications of lipolytic delivery are also discussed.

Technical Abstract: Eicosanoids including epoxyeicosatrienoic acids (EETs) and hydroxyeicosatetraenoic (HETEs) and other oxylipins derived from polyunsaturated fatty acids have emerging roles in endothelial inflammation and its atherosclerotic consequences. Unlike many eicosanoids, they are known to be esterified in cell lipids such as phospholipids and triglycerides but our understanding of these reservoirs is in its infancy. This review focuses on recent work identifying esterified oxylipins in circulation, primarily within lipoproteins, and their effects on parameters of endothelial dysfunction. These oxylipins are known to be released by at least one lipase, lipoprotein lipase, and mediate increased expression of inflammatory markers in endothelial cells which overlap the known roles of lipoproteins in endothelial dysfunction. Challenges to our understanding of this oxylipin compartment including the need to consider the non-arachidonate-derived oxylipins and the implications of lipolytic delivery are also discussed.