Alteration of epoxyeicosatrienoic acids in the liver and kidney of cytochrome P450 4F2 transgenic mice

Zhang, Bijun; Lai, Guangrui; Liu, Xiaoliang; Zhao, Yanyan

doi:10.3892/mmr.2016.5962

Cited by 4 publications

(5 citation statements)

References 24 publications

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“…In addition to prominent roles for eicosanoids in inflammation, they also play important roles in vasal tone and platelet activation. For example, HETEs exhibit prohypertensive effects through vasoconstriction and an antihypertensive effects through natriuresis 48,49 . Platelet activation and apoptotic pathways are increased in PWH, despite virologic suppression 50 , and thrombocytopenia is a common finding in PWH.…”

Section: Discussionmentioning

confidence: 99%

“…For example, HETEs exhibit prohypertensive effects through vasoconstriction and antihypertensive effects through natriuresis. 47 , 48 Platelet activation and apoptotic pathways are increased in PWH, despite virologic suppression, 49 and thrombocytopenia is a common finding in PWH. In addition to roles in vascular and tissue repair, they play central roles in innate immune activation by directly interacting with leukocytes and secreting cytokines and chemokines.…”

Section: Discussionmentioning

confidence: 99%

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Association of Plasma Eicosanoid Levels With Immune, Viral, and Cognitive Outcomes in People With HIV

et al. 2022

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Objective.To determine if plasma eicosanoid levels are associated with immune, viral, and cognitive outcomes in people with the human immunodeficiency virus (PWH).Methods.We measured 42 eicosanoids in a longitudinal study of 95 PWH and 25 demographically comparable uninfected participants. Routine clinical chemistry, virologic, immune markers and a neuropsychological test battery assessing seven cognitive domains was administered to all participants at two study visits over an average of 6.5 months.Results.Plasma eicosanoid concentrations were elevated in PWH (n=95) compared to seronegative controls (n=25) (100% prediction power at 5% FDR, α=0.0531) and in PWH were negatively associated with lower current and nadir CD4 lymphocyte counts. Higher levels of eicosanoids were associated with impairments in working memory, verbal fluency, and executive function. Higher plasma viral load was associated with elevated pro-inflammatory eicosanoids (24% prediction power at 5% FDR, and 42.4% prediction power at 10% FDR, α=0.10). Longitudinal analyses showed that eicosanoid levels were correlated with viral load and with plasma creatinine. Despite associations of eicosanoids with viral loads, elevated plasma eicosanoids were similar in virally suppressed and not-fully suppressed PWH.Conclusions.These data show that HIV infection is associated with a robust production of eicosanoids that is not substantially reduced by antiretroviral therapy (ART). The sustained elevation of these oxylipins in PWH despite ART may contribute to an accelerated aging phenotype that includes earlier than expected brain and peripheral organ damage.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Association of Plasma Eicosanoid Levels With Immune, Viral, and Cognitive Outcomes in People With HIV

et al. 2022

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“…In experimental models, LPS decreases EET while increases 20-HETE ( Anwar-mohamed et al, 2010 ; Theken et al, 2011 ). The importance of the 20-HETE/EET ratio is supported by studies using CYP4F2 transgenic mice ( Zhang et al, 2016 ). In HCC, reduced expression of CYP2A6 modulates the anti-tumor immunity by disrupting the equilibrium between 20-HETE and EETs ( Jiang et al, 2021 ).…”

Section: Biological Functions Of Oxylipins In Liver Disease and Cance...mentioning

confidence: 99%

Eicosanoids and other oxylipins in liver injury, inflammation and liver cancer development

et al. 2023

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Liver cancer is a malignancy developed from underlying liver disease that encompasses liver injury and metabolic disorders. The progression from these underlying liver disease to cancer is accompanied by chronic inflammatory conditions in which liver macrophages play important roles in orchestrating the inflammatory response. During this process, bioactive lipids produced by hepatocytes and macrophages mediate the inflammatory responses by acting as pro-inflammatory factors, as well as, playing roles in the resolution of inflammation conditions. Here, we review the literature discussing the roles of bioactive lipids in acute and chronic hepatic inflammation and progression to cancer.

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“…Recently, it was shown that the dysregulated renal 20‑HETE/EET ratio in the hypertensive Cyp4F2 transgenic mice was resulted from the activation of soluble epoxide hydrolase (sEH) and the inhibition of epoxygenase activity suggesting 20-HETE vasoconstrictive activity. Moreover, 20‑HETE demonstrated an inverse regulatory effect on the endogenous epoxygenases in the kidney [ 89 ].…”

Section: Role Of 20-hete In the Kidneymentioning

confidence: 99%

“…Recently, 20‑HETE demonstrated a counter regulatory effect on the endogenous epoxygenases in the liver. Thus the tuning of 20-HETE and EETs formation and degradation may provide therapeutic benefits; given that they have opposite effects in several diseases [ 89 , 140 ]. Interestingly, 20-HETE level in the urine of cirrhotic patients with ascites is much higher than in case of cirrhosis without ascites which in turn is higher than excretion rates in normal individuals [ 139 ].…”

Section: Role Of 20-hete In the Livermentioning

confidence: 99%

Clinical Implications of 20-Hydroxyeicosatetraenoic Acid in the Kidney, Liver, Lung and Brain: An Emerging Therapeutic Target

et al. 2017

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Cytochrome P450-mediated metabolism of arachidonic acid (AA) is an important pathway for the formation of eicosanoids. The ω-hydroxylation of AA generates significant levels of 20-hydroxyeicosatetraenoic acid (20-HETE) in various tissues. In the current review, we discussed the role of 20-HETE in the kidney, liver, lung, and brain during physiological and pathophysiological states. Moreover, we discussed the role of 20-HETE in tumor formation, metabolic syndrome and diabetes. In the kidney, 20-HETE is involved in modulation of preglomerular vascular tone and tubular ion transport. Furthermore, 20-HETE is involved in renal ischemia/reperfusion (I/R) injury and polycystic kidney diseases. The role of 20-HETE in the liver is not clearly understood although it represents 50%–75% of liver CYP-dependent AA metabolism, and it is associated with liver cirrhotic ascites. In the respiratory system, 20-HETE plays a role in pulmonary cell survival, pulmonary vascular tone and tone of the airways. As for the brain, 20-HETE is involved in cerebral I/R injury. Moreover, 20-HETE has angiogenic and mitogenic properties and thus helps in tumor promotion. Several inhibitors and inducers of the synthesis of 20-HETE as well as 20-HETE analogues and antagonists are recently available and could be promising therapeutic options for the treatment of many disease states in the future.

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Alteration of epoxyeicosatrienoic acids in the liver and kidney of cytochrome P450 4F2 transgenic mice

Cited by 4 publications

References 24 publications

Association of Plasma Eicosanoid Levels With Immune, Viral, and Cognitive Outcomes in People With HIV

Association of Plasma Eicosanoid Levels With Immune, Viral, and Cognitive Outcomes in People With HIV

Eicosanoids and other oxylipins in liver injury, inflammation and liver cancer development

Clinical Implications of 20-Hydroxyeicosatetraenoic Acid in the Kidney, Liver, Lung and Brain: An Emerging Therapeutic Target

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