Metabolic profiling of murine plasma reveals eicosapentaenoic acid metabolites protecting against endothelial activation and atherosclerosis

Liu, Yajin; Fang, Xuan; Zhang, Xu; Huang, Jing; He, Jinlong; Peng, Liyuan; Ye, Chenji; Wang, Yingmei; Xue, Fengxia; Ai, Ding; Li, Dan; Zhu, Yi

doi:10.1111/bph.13971

Cited by 24 publications

(16 citation statements)

References 45 publications

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“…At 12 weeks of age, the mice in the fucoidan group each received an intraperitoneal injection of fucoidan (60 mg kg -1 day -1 ), and the mice in the model group were injected intraperitoneally with physiological saline once per day [28,29]. At 16 weeks of age, all mice were anesthetized using isoflurane and sacrificed by inner canthus artery exsanguination while still anesthetized [30].…”

Section: Animal Models and Ethicsmentioning

confidence: 99%

Fucoidan Inhibits NLRP3 Inflammasome Activation by Enhancing p62/SQSTM1-Dependent Selective Autophagy to Alleviate Atherosclerosis

Cheng

Pan

Wang

et al. 2020

Oxidative Medicine and Cellular Longevity

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NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation contributes to the progression of atherosclerosis, and autophagy inhibits inflammasome activation by targeting macrophages. We investigated whether fucoidan, a marine sulfated polysaccharide derived from brown seaweeds, could reduce NLRP3 inflammasome activation by enhancing sequestosome 1 (p62/SQSTM1)-dependent selective autophagy to alleviate atherosclerosis in high-fat-fed ApoE-/- mice with partial carotid ligation and differentiated THP-1 cells incubated with oxidized low-density lipoprotein (oxLDL). Fucoidan significantly ameliorated lipid accumulation, attenuated progression of carotid atherosclerotic plaques, deregulated the expression of NLRP3 inflammasome, autophagy receptor p62, and upregulated microtubule-associated protein light chain 3 (LC3)-II/I levels. Transmission electron microscopy and GFP-RFP-LC3 lentivirus transfection further demonstrated that fucoidan could activate autophagy. Mechanistically, fucoidan remarkably inhibited NLRP3 inflammasome activation, which was mostly dependent on autophagy. The inhibitory effects of fucoidan on NLRP3 inflammasome were enhanced by autophagy activator rapamycin (Rapa) and alleviated by autophagy inhibitor 3-methyladenine (3-MA). Fucoidan promoted the colocalization of NLRP3 and p62. Knockdown of p62 and ATG5 by small interfering RNA significantly reduced the inhibitory effects of fucoidan treatment on NLRP3 inflammasome. The data suggest that fucoidan can inhibit NLRP3 inflammasome activation by enhancing p62/SQSTM1-dependent selective autophagy to alleviate atherosclerosis.

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Section: Animal Models and Ethicsmentioning

confidence: 99%

Fucoidan Inhibits NLRP3 Inflammasome Activation by Enhancing p62/SQSTM1-Dependent Selective Autophagy to Alleviate Atherosclerosis

Cheng

Pan

Wang

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…Studies show that HEPE tends to present anti-inflammatory effects and 12-HEPE can improve glucose metabolism by promoting glucose uptake through the insulin-like intracellular signaling pathway (Leiria et al, 2019). 18-HEPE, the precursor of the E-series specialized pro-resolving mediators, is another inhibitor of inflammation, and can halt the development of maladaptive cardiac remodeling and atherosclerosis (Endo et al, 2014;Liu et al, 2018). 16,17-EpDPE derived from DHA is a vasodilator which regulates the calcium-potassium (BK) channel in arterial smooth muscle cells and correlates with the decrease of white matter hyperintensity in older populations with a high risk of dementia (Wang et al, 2011;Shinto et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Quantitative Profiling of Oxylipins in Acute Experimental Intracerebral Hemorrhage

et al. 2020

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Oxylipins are a series of bioactive lipid metabolites derived from polyunsaturated fatty acids that are involved in cerebral homeostasis and the development of intracerebral hemorrhage (ICH). However, comprehensive quantification of the oxylipin profile in ICH remains unknown. Therefore, an ICH mouse model was constructed and liquid chromatography tandem mass spectrometry was then performed to quantify the change in oxylipins in ICH. The expression of the oxylipin relative enzymes was also reanalyzed based on RNA-seq data from our constructed ICH dataset. A total of 58 oxylipins were quantifiable and the levels of 17 oxylipins increased while none decreased significantly in the first 3 days following ICH. The most commonly increased oxylipins in ICH were derived from AA (10/17) and EPA (4/17) followed by LA (2/17) and DHA (1/17). 18-HEPE from EPA was the only oxylipin that remained significantly increased from 0.5 to 3 days following ICH. Furthermore, 14 of the increased oxylipins reached a peak level on the first day of ICH, and soon decreased while five oxylipins (PGJ2, 15-oxo-ETE, 12-HEPE, 18-HEPE, and 5-oxo-ETE) had increased 3 days after ICH suggesting that the profile shifted with the progression of ICH. In our constructed RNA-seq dataset based on ICH rats, 90 oxylipin relative molecules were detected except for COX. Among these, Cyp4f18, Cyp1b1, Cyp2d3, Cyp2e1, Cyp1a1, ALOX5AP, and PLA2g4a were found up-regulated and Cyp26b1 was found to decrease in ICH. In addition, there was no significant change in sEH in ICH. This study provides fundamental data on the profile of oxylipins and their enzymes in ICH. We found that the profile shifted as the progression of ICH and the metabolism of arachidonic acid and eicosapentaenoic acid was highly affected in ICH, which will help further studies explore the functions of oxylipins in ICH.

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“…RvE1 can ameliorate atherosclerosis ( Salic et al, 2016 ). In addition, 18-HEPE and 17,18-EEQ ameliorated endothelial-cell activation and monocyte adhesion by inhibiting the TNFα-induced NF-κB pathway ( Liu et al, 2018 ).…”

Section: Effect Of ω-3 Pufa-derived Oxylipins On Atherosclerosismentioning

confidence: 99%

Effect of ω-3 Polyunsaturated Fatty Acids-Derived Bioactive Lipids on Metabolic Disorders

2021

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Arachidonic acid (ARA) is an important ω-6 polyunsaturated fatty acid (PUFA), and docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and n-3 docosapentaenoic acid (n-3 DPA) are three well-known ω-3 PUFAs. These fatty acids can be metabolized into a number of bioactive lipids. Eicosanoids derived from ARA have drawn great attention because of their important and complex biofunctions. Although EPA, DHA and n-3 DPA have also shown powerful biofunctions, we have fewer studies of metabolites derived from them than those from ARA. Recently, growing research has focused on the bioaction of ω-3 PUFA-derived metabolites, which indicates their great potential for treating metabolic disorders. Most of the functional studies of these bioactive lipids focused on their anti-inflammatory effects. However, several studies elucidated their direct effects on pancreatic β cells, hepatocytes, adipocytes, skeletal muscle cells, and endothelial cells. These researches revealed the importance of studying the functions of metabolites derived from ω-3 polyunsaturated fatty acids other than themselves. The current review summarizes research into the effects of ω-3 PUFA-derived oxylipins on metabolic disorders, including diabetes, non-alcoholic fatty liver disease, adipose tissue dysfunction, and atherosclerosis.

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Metabolic profiling of murine plasma reveals eicosapentaenoic acid metabolites protecting against endothelial activation and atherosclerosis

Abstract: This article is part of a themed section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc.

Cited by 24 publications

References 45 publications

Fucoidan Inhibits NLRP3 Inflammasome Activation by Enhancing p62/SQSTM1-Dependent Selective Autophagy to Alleviate Atherosclerosis

Fucoidan Inhibits NLRP3 Inflammasome Activation by Enhancing p62/SQSTM1-Dependent Selective Autophagy to Alleviate Atherosclerosis

Quantitative Profiling of Oxylipins in Acute Experimental Intracerebral Hemorrhage

Effect of ω-3 Polyunsaturated Fatty Acids-Derived Bioactive Lipids on Metabolic Disorders

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