Endogenously Generated Omega‐3 Fatty Acids Attenuate Vascular Inflammation and Neointimal Hyperplasia by Interaction With Free Fatty Acid Receptor 4 in Mice

Li, Xinzhi; Ballantyne, Laurel L.; Che, Xinghui; Mewburn, Jeffrey; Kang, Jing; Barkley, Robert M.; Murphy, Robert C.; Yu, Ying; Funk, Colin D.

doi:10.1161/jaha.115.001856

Cited by 31 publications

(22 citation statements)

References 68 publications

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“…Urinary Tx-M and TxB 2 detected in plasma and serum clearly indicate that platelets are the main source of TxA 2 , and platelet COX-1's coupling with TBXAS cannot be compensated by COX-2, perhaps triggering a rapid degradation of the knock-in COX-2 or a limited access to TBXAS. The local concentration of AA in human platelets can be up to 50 M (55) and approximately 25 M in mouse serum (56), which is substantially high to preferentially "cooperate" with COX-1, as discussed above. In this case, these two isoforms show no interchangeability, obviously because of the absence of COX-2 (native or knock-in) expression in platelets.…”

Section: Discussionmentioning

confidence: 88%

Flipping the cyclooxygenase (Ptgs) genes reveals isoform-specific compensatory functions ,

Mazaleuskaya

Yuan

et al. 2018

Journal of Lipid Research

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Two prostaglandin (PG) H synthases encoded by genes, colloquially known as cyclooxygenase (COX)-1 and COX-2, catalyze the formation of PG endoperoxide H, the precursor of the major prostanoids. To address the functional interchangeability of these two isoforms and their distinct roles, we have generated COX-2>COX-1 mice whereby is knocked in to the locus. We then "flipped" genes to successfully create the Reversa mouse strain, where knock-in COX-2 is expressed constitutively and knock-in COX-1 is lipopolysaccharide (LPS) inducible. In macrophages, flipping the two genes has no obvious impact on COX protein subcellular localization. COX-1 was shown to compensate for PG synthesis at high concentrations of substrate, whereas elevated LPS-induced PG production was only observed for cells expressing endogenous COX-2. Differential tissue-specific patterns of expression of the knock-in proteins were evident. Thus, platelets from COX-2>COX-1 and Reversa mice failed to express knock-in COX-2 and, therefore, thromboxane (Tx) production in vitro and urinary Tx metabolite formation in COX-2>COX-1 and Reversa mice in vivo were substantially decreased relative to WT and COX-1>COX-2 mice. Manipulation of COXs revealed isoform-specific compensatory functions and variable degrees of interchangeability for PG biosynthesis in cells/tissues.

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Section: Discussionmentioning

confidence: 88%

Flipping the cyclooxygenase (Ptgs) genes reveals isoform-specific compensatory functions ,

Mazaleuskaya

Yuan

et al. 2018

Journal of Lipid Research

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“…Studies in fat-1 transgenic mice have strengthened the previous information, observinga drop in the macrophage migration markers into the adipose tissue of these mice as compared with the matched wild type group fed with a HFD [158], together with an induction of a phenotypic shift from the pro-inflammatory M1 macrophages to the anti-inflammatory M2 macrophages [61,62](see Table 2). …”

Section: (B) Reduction Of M1 Macrophages Infiltration and Promotion Omentioning

confidence: 75%

Omega-3 fatty acids and adipose tissue function in obesity and metabolic syndrome

Martínez-Fernández

Laiglesia

Huerta

et al. 2015

Prostaglandins & Other Lipid Mediators

179

128

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“…On some slides, CD68 was stained fluorescently. To visualize the arterial intima and media layers, immunofluorescence staining of AA and the surrounding PVAT was performed by incubation of sections with primary antibodies directed against mouse CD31 (FITC conjugated, 1:200, 102506; BioLegend, San Diego, CA, USA), and SMαA (FITC conjugated, 1:200, F3777; MilliporeSigma), as previously described (25).…”

Section: Methodsmentioning

confidence: 99%

Perivascular adipose tissue–derived extracellular vesicle miR‐221‐3p mediates vascular remodeling

Ballantyne²,

et al. 2019

The FASEB Journal

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Adipose tissue–secreted extracellular vesicles (EVs) containing microRNAs (miRNAs) convey intercellular message signaling. The biogenesis of EV‐miRNAs from perivascular adipose tissue (PVAT) and their roles in intercellular communication in response to obesity‐associated inflammation have not yet been fully explored. By feeding mice a high‐fat diet for 16 wk, we established obesity‐associated, chronic low‐grade inflammation in PVAT, characterized as hypertrophy of perivascular adipocytes, decreased adipogenesis, and proinflammatory macrophage infiltration. We show that PVAT‐derived EVs and their encapsulated miRNAs can be taken up into vascular smooth muscle cells (VSMCs) in vivo and in vitro. miR‐221‐3p is one of the highly enriched miRNAs in obese PVAT and PVAT‐derived EVs. Transfer and direct overexpression of miR‐221‐3p dramatically enhances VSMC proliferation and migration. Peroxisome proliferator–activated receptor γ coactivator 1α is identified as a miR‐221‐3p target in VSMC phenotypic modulation. Obese mice secrete abundant miRNA‐containing EVs, evoking inflammatory responses in PVAT and vascular phenotypic switching in abdominal aorta of lean mice. Local delivery of miR‐221‐3p mimic in femoral artery causes vascular dysfunction by suppressing the contractile genes in the arterial wall. Our findings provide an EV–miR‐221‐3p–mediated mechanism by which PVAT triggers an early‐stage vascular remodeling in the context of obesity‐associated inflammation.—Li, X., Ballantyne, L. L., Yu, Y., Funk, C. D. Perivascular adipose tissue–derived extracellular vesicle miR‐221‐3p mediates vascular remodeling. FASEB J. 33, 12704–12722 (2019). http://www.fasebj.org

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Endogenously Generated Omega‐3 Fatty Acids Attenuate Vascular Inflammation and Neointimal Hyperplasia by Interaction With Free Fatty Acid Receptor 4 in Mice

Cited by 31 publications

References 68 publications

Flipping the cyclooxygenase (Ptgs) genes reveals isoform-specific compensatory functions ,

Flipping the cyclooxygenase (Ptgs) genes reveals isoform-specific compensatory functions ,

Omega-3 fatty acids and adipose tissue function in obesity and metabolic syndrome

Perivascular adipose tissue–derived extracellular vesicle miR‐221‐3p mediates vascular remodeling

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