The emerging role of oxylipins in thrombosis and diabetes

Abstract

The prevalence of cardiovascular disease (CVD), the leading cause of death in the US, is predicted to increase due to the shift in age of the general population and increase in CVD risk factors such as obesity and diabetes. New therapies are required to decrease the prevalence of CVD risk factors (obesity and diabetes) as well as reduce atherothrombosis, the major cause of CVD related mortality. Oxylipins, bioactive metabolites derived from the oxygenation of polyunsaturated fatty acids, play a role in the progression of CVD risk factors and thrombosis. Aspirin, a cyclooxygenase-1 inhibitor, decreases atherothrombotic associated mortality by 25%. These potent effects of aspirin have shown the utility of modulating oxylipin signaling pathways to decrease CVD mortality. The role of many oxylipins in the progression of CVD, however, is still uncertain or controversial. An increased understanding of the role oxylipins play in CVD risk factors and thrombosis could lead to new therapies to decrease the prevalence of CVD and its associated mortality.

Oleocanthal-rich extra virgin olive oil demonstrates acute anti-platelet effects in healthy men in a randomized trial

“…Platelet aggregation is regulated by a number of mediators, including COX-derived TXB2, platelet 12-LOX-derived 12-HETE, and 15-LOX-derived 15-HETE (Tourdot et al, 2013). While no changes in these, and other COX and LOX-derived mediators were observed in all subjects following EVOO consumption, “responders” did demonstrate a reduction in plasma TXB2, 11-HETE and 15-HETE concentrations following consumption of both D2 i 0.5 and D2 i 2, compared to D2 i 0.…”

“…Treatment and subject orders were considered and had no effect on regression results. Oxylipins used in the regression model have been associated with platelet function (Tourdot et al, 2013), and included the sum of the COX products thromboxane B2 (TXB2), prostaglandin E2 (PGE2) and 11-hydroxyeicosatetraenoic acid (11-HETE), and the LOX products 12-HETE, 15-HETE (collectively referred to as Δ[COX + LOX]). Individual phenolics used in the regression model were oleocanthal, oleacein, and tyrosol as the mg/kg of body weight dose of these phenolics were > 0.1 mg/kg for at least one EVOO consumed.…”

“…The best known of these associated with clot formation is thromboxane, whose production is targeted through the inhibition of COX with aspirin. In addition, oxylipins produced from lipoxygenase (LOX) and cytochrome P450 may be also have roles in platelet activation and inflammatory modulation (Tourdot, Ahmed, & Holinstat, 2013). …”

Antioxidant supplementation and obesity have independent effects on hepatic oxylipin profiles in insulin-resistant, obesity-prone rats

“…The altered production of oxygenated, bioactive polyunsaturated fatty acids (PUFAs) (i.e., oxylipins) in obesity may have pathological consequences, and a number of recent studies have investigated the mediation of obesity-induced insulin resistance by oxylipins [5][6][7][8][9]. Oxylipins include a myriad of species derived from n6 PUFA, such as arachidonic acid (ArA; 20:4n6) and linoleic acid (LA; 18:2n6), and from n3 PUFA, such as α-linolenic acid (ALA; 18:3n3), eicosapentaenoic acid (EPA; 20:5n3), and docosahexaenoic acid (DHA; 22:6n3).…”

“…Oxylipins include a myriad of species derived from n6 PUFA, such as arachidonic acid (ArA; 20:4n6) and linoleic acid (LA; 18:2n6), and from n3 PUFA, such as α-linolenic acid (ALA; 18:3n3), eicosapentaenoic acid (EPA; 20:5n3), and docosahexaenoic acid (DHA; 22:6n3). Bioactivity Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/freeradbiomed among known oxylipins varies with structure and includes pro-and anti-inflammatory actions, vasodilatory/relaxant properties, and mediation of cell growth and proliferation [9]. These lipid mediators include products derived from cyclooxygenases (COX), lipoxygenases (LOX), and cytochrome P450 (CYP)-mediated oxygenation, as well as products derived from free-radical-catalyzed PUFA oxidation [9].…”