The roles of CYP450 epoxygenases and metabolites, epoxyeicosatrienoic acids, in cardiovascular and malignant diseases

Xu, Xizhen; Zhang, Xin A.; Wang, Dao Wen

doi:10.1016/j.addr.2011.03.006

Cited by 182 publications

(170 citation statements)

References 116 publications

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“…Biological activities of EETs and the opposing actions of 20-HETE within the heart are now well established (6). EETs can be applied to a variety of ion channels of cardiovascular cells, and protect myocardial cells by regulating the expression of genes and proteins associated with apoptosis (20). 20-HETE has detrimental effects, particularly in the heart ischemia.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, EETs may have a key role during the development and/or progression of KD and DCM. CYP2C are the predominant epoxygenase isoforms involved in EETs formation, and they are abundantly expressed in the endothelium, myocardium and kidney in humans (20). As a consequence, the CYP2C19 gene was upregulated and the frequent protein expression may be a protective compensation reaction.…”

Section: Discussionmentioning

confidence: 99%

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Metabolism of arachidonic acid by the cytochrome P450 enzyme in patients with chronic Keshan disease and dilated cardiomyopathy

Zhou

Wang

et al. 2015

Biomedical Reports

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Abstract. Keshan disease (KD) is an endemic cardiomyopathy. The etiology of KD is selenium deficiency; however, it is not the only one and there is no effective approach to preventing and curing this disease. The aim of the present study was to explore the differences in the role of arachidonic acid (AA) by the cytochrome P450 enzyme between chronic KD (CKD), dilated cardiomyopathy (DCM) and control patients. Reverse transcription-quantitative polymerase chain reaction was used to detect the CYP1A1 and CYP2C19 gene expression levels in 6 CKD patients, 6 DCM and 6 healthy controls. An enzyme-linked immunosorbent assay kit was applied to detect serum protein expression of CYP1A1 and CYP2C19, AA and epoxyeicosatrienoic acids (EETs), and 20-hydroxyeicosatetraenoic acids (20-HETE) in 67 CKD patients, 28 DCM, and 58 controls. The present results showed that the expression levels of CYP1A1 and CYP2C19 genes were significantly upregulated compared with the control group (P<0.01). The expression level of the CYP1A1 protein in the CKD (49.55±35.11 pg/ml) and DCM (46.68 ±13.01 pg/ml) groups were enhanced compared with the control group (44.33±16.76 pg/ml) (P<0.01). The production of the CYP2C19 protein in the CKD (57.52±28.22 pg/ml) and DCM (56.36±11.26 pg/ml) groups was enhanced compared with the control group (51.43±10.76 pg/ml). The concentrations of AA in the CKD (126.27±47.91 ng/ml) and DCM (133.24±58.67 ng/ml) groups were also significantly increased compared to the control (78.16±23.90 ng/ml) (P<0.001). The concentration of 20-HETE in the CKD (198.34±17.22 ng/ml) and DCM (194.46±20.35 ng/ml) groups were also significantly increased compared to the control (130.10±16.10 ng/ml) (P<0.001). The only difference between CKD and DCM was for the expression of the CYP1A1 gene and protein.The maximum concentration of EETs was in the control group (44.37±6.14 pg/ml), and the other two groups were lower than the control group (P<0.001). These findings indicated that AA-derived CYP450 metabolites may have a critical role in the pathogenesis of KD and DCM. Upregulation of the CYP2C19 gene and frequent protein expression may be a protective compensation reaction, while CYP1A1 may aggravate myocardial injury.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Metabolism of arachidonic acid by the cytochrome P450 enzyme in patients with chronic Keshan disease and dilated cardiomyopathy

Zhou

Wang

et al. 2015

Biomedical Reports

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“…Arachidonic acid is a polyunsaturated -6 fatty acid produced in mammalian tissues and absorbed through dietary sources. Once released from the phospholipids by phospholipases, arachidonic acid is converted to endogenous bioactive eicosanoids by three different classes of enzymes, including CYPs belonging to CYP2C, CYP2J, and CYP4F families (11)(12)(13)(14)(15)(16). The four EET regioisomers formed by epoxygenation reactions are 5,6-, 8,9-, 11,12-, and 14 -15-EETs.…”

Section: Discussionmentioning

confidence: 99%

Targeting of Splice Variants of Human Cytochrome P450 2C8 (CYP2C8) to Mitochondria and Their Role in Arachidonic Acid Metabolism and Respiratory Dysfunction

Bajpai

Srinivasan

Ghosh

et al. 2014

Journal of Biological Chemistry

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“…Hence, the increased ratio of 11-dehydroTXB2/6-Keto PGF1a in hypothyroid patients may represent a shift toward vasoconstriction. Numerous studies have shown that many eicosanoids play key roles in the development of atherosclerosis and are new biomarkers and drug therapy targets [20][21][22][23] . Therefore, whether the eicosanoid profile in SH patients is abnormal and associated with susceptibility to cardiovascular, cerebrovascular and other serious diseases and whether L-T4 replacement therapy (LTR) can affect the eicosanoid profile need to be studied further.…”

Section: Wwwchinapharcom Zhang Y Et Almentioning

confidence: 99%

Thyroxine therapy ameliorates serum levels of eicosanoids in Chinese subclinical hypothyroidism patients

Zhang

et al. 2016

Acta Pharmacol Sin

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Aim: The eicosanoids derived from phospholipids play key roles in inflammation. However, the profiles of serum eicosanoids in subclinical hypothyroidism (SH) patients and the effects of thyroxine replacement therapy (TRT) on these eicosanoids remain unclear. Many studies show that TSH regulates lipid metabolism. As eicosanoids derived from phospholipids play key roles in oxidative stress and immune function and inflammatory process, it was necessary to explore the profiles of serum eicosanoids in SH patients and the effects of thyroxine replacement therapy (TRT) on the eicosanoids. Methods: A total of 50 Chinese SH patients and 22 healthy volunteers were recruited. SH patients received TRT (L-T4, 25 and 50 mcg/d for patients with TSH≤10.0 mIU/L and TSH>10.0 mIU/L, respectively) for 3 months. Serum levels of major eicosanoids and cPLA2 were analyzed using LC-MS and clinical biochemical assays. Results: The serum levels of cPLA2, eicosanoids (8-isoPGF2a, 11-dehydroTXB2 and 12-HETE) and 11-dehydroTXB2/6-Keto-PGF1a were significantly elevated in SH patients. The serum TSH levels were significantly correlated with the levels of cPLA2 (r=+0.65), 11-dehydroTXB2 (r=+0.32) and 11-dehydroTXB2/6-Keto-PGF1a (r=+0.37). After 3-month TRT, the serum levels of TSH, cPLA2 and the above-mentioned eicosanoids in SH patients were significantly decreased. Conclusion: The metabolism of eicosanoids is significantly altered in Chinese SH patients, and TRT can ameliorate the abnormalities of serum eicosanoid levels.

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The roles of CYP450 epoxygenases and metabolites, epoxyeicosatrienoic acids, in cardiovascular and malignant diseases

Cited by 182 publications

References 116 publications

Metabolism of arachidonic acid by the cytochrome P450 enzyme in patients with chronic Keshan disease and dilated cardiomyopathy

Metabolism of arachidonic acid by the cytochrome P450 enzyme in patients with chronic Keshan disease and dilated cardiomyopathy

Targeting of Splice Variants of Human Cytochrome P450 2C8 (CYP2C8) to Mitochondria and Their Role in Arachidonic Acid Metabolism and Respiratory Dysfunction

Thyroxine therapy ameliorates serum levels of eicosanoids in Chinese subclinical hypothyroidism patients

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