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Editorial
. 2020 Apr;31(2):104-107.
doi: 10.1097/MOL.0000000000000666.

Editorial: Nitro-fatty acids: novel drug candidates for the co-treatment of atherosclerosis and nonalcoholic fatty liver disease

Oren Rom  1 , Yuhao Liu  1 , Lin Chang  1 , Y Eugene Chen  1 , Michael Aviram  2
Affiliations
Editorial

Editorial: Nitro-fatty acids: novel drug candidates for the co-treatment of atherosclerosis and nonalcoholic fatty liver disease

Oren Rom et al. Curr Opin Lipidol. 2020 Apr.
No abstract available

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Conflict of interest statement

Conflicts of interest: There are no conflicts of interest.

Figures

Fig. 1.
Fig. 1.. NO2-FAs for the co-treatment of atherosclerosis and NAFLD: molecular and metabolic mechanisms.
ALT, alanine aminotransferase; AST, aspartate aminotransferase; COL1A, collagen, type I, alpha; CTGF, connective tissue growth factor; GCLC, glutamate-cysteine ligase catalytic subunit; GCLM, glutamate-cysteine ligase regulatory subunit; GPAT2, glycerol-3-phosphate acyltransferase-2; GSH, glutathione; GSR, glutathione reductase; HMOX1, heme oxygenase-1; ICAM1, intercellular adhesion molecule-1; IL-6, interleukin 6; MCP-1, monocyte chemoattractant protein-1; NAFLD, non-alcoholic fatty liver disease; NF-κB, nuclear factor kappa B; NQO1, NAD(P)H quinone dehydrogenase-1; Nrf2, nuclear factor erythroid 2-related factor-2; OxLDL, oxidized low-density lipoprotein; PON2, paraoxonase-2; ROS, reactive oxygen species; SCD-1, stearoyl-CoA desaturase-1; SREBF1, sterol regulatory element-binding transcription factor-1; SREBP1, sterol regulatory element-binding protein-1; STAT-1, signal transducer and activator of transcription-1; TGFB1, transforming growth factor beta-1; TIMP1, TIMP metallopeptidase inhibitor-1; TLR, toll-like receptor; Tumor necrosis factor; VCAM1, vascular cell adhesion molecule-1.
Fig. 2.
Fig. 2.. NO2-OA prevents Western diet-induced atherosclerosis in Apoe−/− mice.
Male Apoe−/− mice were fed standard chow diet or Western diet (Envigo TD.88137, 42% fat and 0.2% cholesterol) for 8 weeks and treated with 8 mg/kg/day of NO2-OA via subcutaneously implanted osmotic mini-pumps. Mice fed chow diet and administrated vehicle (polyethylene glycol) as well as mice fed Western diet and administrated vehicle or 8 mg/kg/d of non-nitrated OA were served as controls. Oil Red O staining was used for en face analysis of atherosclerotic lesions in the aortic tree. Representative aortas from each experimental group are shown. Statistical differences were compared by one-way ANOVA followed by Bonferroni post-hoc test (n=8 mice per group).
See this image and copyright information in PMC

References

REFERENCES AND RECOMMENDED READING

    1. Schopfer FJ, Lin Y, Baker PR, et al. Nitrolinoleic acid: an endogenous peroxisome proliferator-activated receptor gamma ligand. Proc Natl Acad Sci U S A. 2005;102(7):2340–2345. - PMC - PubMed
    1. Cui T, Schopfer FJ, Zhang J, et al. Nitrated fatty acids: Endogenous anti-inflammatory signaling mediators. J Biol Chem. 20064;281(47):35686–35698. - PMC - PubMed
    1. Kansanen E, Bonacci G, Schopfer FJ, et al. Electrophilic nitro-fatty acids activate NRF2 by a KEAP1 cysteine 151-independent mechanism. J Biol Chem. 2011;286(16):14019–14027. - PMC - PubMed
    1. Villacorta L, Chang L, Salvatore SR, et al. Electrophilic nitro-fatty acids inhibit vascular inflammation by disrupting LPS-dependent TLR4 signalling in lipid rafts. Cardiovasc Res. 2013;98(1):116–124. - PMC - PubMed
    1. Villacorta L, Minarrieta L, Salvatore SR, et al. In situ generation, metabolism and immunomodulatory signaling actions of nitro-conjugated linoleic acid in a murine model of inflammation. Redox Biol. 2018;15:522–531. - PMC - PubMed

    2. * This study demonstrated formation, metabolism, anti-inflammatory and anti-oxidant properties of NO2-CLA under inflammatory conditions. Macrophages activated with LPS/IFN-γ were shown to mediate CLA nitration via inducible nitric oxide synthase (iNOS) activity. In situ NO2-CLA formation was also demonstrated using a mouse model of zymosan-A induced peritonitis. In turn, administration of exogenous NO2-CLA as well as endogenous NO2-CLA inhibited the transcription of NF-κB-dependent genes and activated Nrf2 signaling, leading to suppression of pro-inflammatory cytokine production and over-expression of cytoprotective phase 2 proteins.

FURTHER RECOMMENDED READING
    1. Kelley EE, Baust J, Bonacci G, et al. Fatty acid nitroalkenes ameliorate glucose intolerance and pulmonary hypertension in high-fat diet-induced obesity. Cardiovasc Res. 2014;101(3):352–363. - PMC - PubMed
    1. Zhang J, Villacorta L, Chang L, et al. Nitro-oleic acid inhibits angiotensin II-induced hypertension. Circ Res. 2010;107(4):540–548. - PMC - PubMed
    1. Rudolph V, Rudolph TK, Schopfer FJ, et al. Endogenous generation and protective effects of nitro-fatty acids in a murine model of focal cardiac ischaemia and reperfusion. Cardiovasc Res. 2010;85(1):155–166. - PMC - PubMed
    1. Cole MP, Rudolph TK, Khoo NK, et al. Nitro-fatty acid inhibition of neointima formation after endoluminal vessel injury. Circ Res. 2009;105(10):965–972 - PMC - PubMed
    1. Villacorta L, Zhang J, Garcia-Barrio MT, et al. Nitro-linoleic acid inhibits vascular smooth muscle cell proliferation via the Keap1/Nrf2 signaling pathway. Am J Physiol Heart Circ Physiol. 2007;293(1):H770–776. - PMC - PubMed

    2. In 2018, the ‘nitro-lipids series’ was published in the journal Nitric Oxide, summarizing the body of knowledge on different aspects of NO2-FAs accumulated during the last two decades. Below are key reviews relevant to NO2-FA discovery, signaling actions, roles in cardiovascular and metabolic diseases as well as potential clinical applicability:

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