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About the Authors:
John W. Newman
Affiliations USDA, ARS, WHNRC, Obesity and Metabolism Research Unit, Davis, CA, United States of America, Department of Nutrition, University of California Davis, Davis, CA, United States of America
Theresa L. Pedersen
Affiliation: USDA, ARS, WHNRC, Obesity and Metabolism Research Unit, Davis, CA, United States of America
Verdayne R. Brandenburg
Affiliation: Family Medicine, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, United States of America
William S. Harris
Affiliation: Internal Medicine, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, United States of America
Gregory C. Shearer
* E-mail: [email protected]
Affiliations Internal Medicine, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, United States of America, Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, United States of America, Cardiovascular Health Research Center, Sanford Research/USD, Sioux Falls, South Dakota, United States of America, Department of Nutritional Sciences, The Pennsylvania State University, University Park, Pennsylvania, United States of America
Introduction
The control of LDL-C is effective in reducing cardiovascular disease (CVD; see list of abbreviations, File S3) [1]–[3], however other components of risk have yet to be effectively managed, including inflammation and impaired endothelial function. Fatty acids (FA) play an important role in these processes. Polyunsaturated FAs undergo modification into oxylipins, an important superclass of lipid mediators which includes the arachidonic acid (AA)-derived eicosanoids. These autacoids are primarily generated by one of three enzymatic pathways: cyclooxygenases (COXs) which generate the prostanoids and thromboids; lipoxygenases (LOXs) which generate leukotrienes, resolvins, hepoxilins and mid-chain alcohols; and cytochrome p450s (CYPs) which generate epoxides and omega-terminal alcohols [4].
Oxylipins are potent mediators of inflammation and vascular function, and their potencies can vary by parent FA [5]–[7]. While most in vivo studies have focused on AA-metabolites, we have shown that the administration of prescription omega-3 fatty acids (P-OM3) can reduce the abundance of oxylipins derived from AA, while increasing the abundance of eicosapentaenoate- (EPA) and docosahexaenoate- (DHA) derived oxylipins [8], [9]. Oxylipins are generally considered to act locally, however their presence in plasma suggests they act in an endocrine fashion as well. In rats, most oxylipins (>90% of those present in plasma) are found acylated in the glycerolipids of lipoproteins [10]. While the...