Quantitative profiling of oxylipins in plasma and atherosclerotic plaques of hypercholesterolemic rabbits

Abstract

Oxylipins are oxidation products of polyunsaturated fatty acids (PUFAs) that affect a broad range of physiological processes, including cell proliferation, inflammation, inflammation resolution, and vascular function. Moreover, oxylipins are readily detectable in plasma, and certain subsets of oxylipins have been detected in human atherosclerotic lesions. Taken together, we set out to produce a detailed quantitative assessment of plasma and plaque oxylipins in a widely used model of atherosclerosis, to identify potential biomarkers of disease progression. We administered regular chow or regular chow supplemented with 0.5% cholesterol (HC) to male New Zealand white rabbits for 12 weeks to induce hypercholesterolemia and atherosclerosis. Our targeted lipidomic analyses of oxylipins on plaques isolated from rabbits fed the HC diet detected 34 oxylipins, 28 of which were in compliance with our previously established quality control acceptance criteria. The arachidonic acid (AA) metabolite derived from the COX pathway, 6-keto-PGF1α was the most abundant plaque oxylipin, followed by the linoleic acid (LA) metabolites 9-HODE, 13-HODE and 9,12,13-TriHOME and the arachidonic acid (AA)-derivatives 11-HETE and 12-HETE. We additionally found that the most abundant oxylipins in plasma were three of the five most abundant oxylipins in plaque, namely 11-HETE, 13-HODE, and 9-HODE. The studies reported here make the first step towards a comprehensive characterization of oxylipins as potentially translatable biomarkers of atherosclerosis.

Linoleic acid derived oxylipins are elevated in kidney and liver and reduced in serum in rats given a high-protein diet

“…These studies show that HP can change one class of oxylipin (prostaglandins) in the kidney that could exert adverse effects on kidney. Liver is the key site of protein metabolism and liver and blood oxylipins have been associated with a number of diseased liver conditions and other disorders [22][23][24][25][26][27][28], but these also have not been examined in the context of HP diets.…”

“…In particular, DiHOMEs exert cytotoxicity in renal proximal tubular cells [147,148] and are involved in a variety of pathophysiological consequences including inducing chemotaxis, inflammation, cardiovascular disease and pulmonary diseases [149][150][151][152]. Other LA derived oxylipins such as HODE and oxoODEs play roles in oxidative stress, vasodilation, proliferation and inflammation and in the pathogenesis of atherosclerosis [27,126,153,154]. Some LA derived oxylipins in serum are associated with pain and Achilles tendinopathy [28,155], and lower levels of 13-HODE have been reported in colon and lung cancer [156,157].…”

New insights into the effects of onion consumption on lipid mediators using a diet-induced model of hypercholesterolemia

“…A limitation in the results is that it is possible that responses in the oxylipin pattern found in this hypercholesterolemic model may not be reproduced in other species ( e.g. [41],). Thus, the modulation of oxylipins induced by supplementation with onion should be studied for each individual model, taking also into account the specific influence and response to the basal diets.…”

Garlic Supplementation Modified Enzymatic Omega‐6 Polyunsaturated Fatty Acid Oxidation in Mild Hypercholesterolemia

“…However, the ambiguous biosynthesis of 9‐HETE and 11‐HETE involves both cytochrome P450 dependent oxygenation and lipid peroxidation . Insofar, the role of 9‐ and 11‐HETE is suggested to involve in generic inflammation, atherosclerosis, ischemia, and myocardial infarction, which are conditions highly related to the risk of disease development in patients with hypercholesterolemia.…”