Am J Physiol Heart Circ Physiol, 2017, doi: 10.1152/ajpheart.00201.2017.

Dietary Modulation of Oxylipins in Cardiovascular Disease and Aging.

Caligiuri, SPB. Parikh, M. Stamenkovic, A. Pierce, GN. Aukema, HM.

Key Findings

Oxylipins are an important group of fatty acid metabolites amenable to dietary manipulation.  Due to the role they play in cardiovascular disease and in age-related degeneration, oxylipins are gaining recognition as viable targets for specific dietary interventions focused on manipulating oxylipin composition to control these biological processes. All tissues in the body contain 51 oxylipins, which are bioactive lipids that are endogenously produced via the oxygenation of polyunsaturated fatty acids. Their involvement in cardiovascular disease and aging includes their roles in innate immunity, inflammation, cardiac function, blood coagulation and vascular tone regulation. This review highlights the physiological and pathophysiological role of oxylipins in cardiovascular disease and aging, as well as how concentrations of oxylipins can be altered nutritionally. The review indicates that the effect of dietary ω-3 fatty acids on the production of oxylipins plays an important role in the mechanisms by which these dietary fatty acids reduce cardiovascular risk. Recent findings of dietary ALA effects on oxylipins in hypertensive patients suggest that ALA may affect cardiovascular risk via unique effects on oxylipins. Given the diverse functions and potencies of the different oxylipins and those derived from different fatty acids, comprehensive profiling of oxylipins in multiple tissues is necessary to appreciate the overall biological effects of the balance of these bioactive lipids. In this regard, studies comparing the biological effects of individual and combined oxylipins in multiple organ systems will enhance understanding of oxylipin functions in whole organisms.

ABSTRACT:

Oxylipins are a group of fatty acid metabolites generated via oxygenation of polyunsaturated fatty acids and are involved in processes such as inflammation, immunity, pain, vascular tone and coagulation. As a result, oxylipins are implicated in many conditions characterized by these processes including cardiovascular disease and aging. The best characterized oxylipins in relation to cardiovascular disease are derived from the ω-6 fatty acid arachidonic acid. These oxylipins generally increase inflammation, hypertension and platelet aggregation, although not universally. Similarly, oxylipins derived from the ω-6 fatty acid linoleic acid generally have more adverse than beneficial cardiovascular effects. Alternatively, most oxylipins derived from the 20- and 22-carbon ω-3 fatty acids have anti-inflammatory, anti-aggregatory and vasodilatory effects that help explain the cardioprotective effects of these fatty acids. Much less is known regarding the oxylipins derived from the 18-carbon ω-3 fatty acid, α-linolenic acid, but clinical trials with flaxseed supplementation indicate that these oxylipins can have positive effects on blood pressure. Normal aging also is associated with changes in oxylipin levels in the brain, vasculature and other tissues, indicating that oxylipin changes with aging may be involved in age-related changes in these tissues. A small number of trials in humans and animals with interventions that contain either the 18-carbon or the 20- and 22-carbon ω-3 fatty acids indicate that dietary-induced changes in oxylipins may be beneficial in slowing the changes associated with normal aging. In summary, oxylipins are an important group of molecules amenable to dietary manipulation to target cardiovascular disease and age-related degeneration.

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