title: Metabolism of arachidonic acid by the cytochrome P450 enzyme in patients with chronic Keshan disease and dilated cardiomyopathy.
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.
authors.affiliation: School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases National Health and Family Planning Commission, Xi'an, Shaanxi 710061, P.R. China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China.
authors.forename: Shulan
authors.initials: S
authors.lastname: He
authors.affiliation: School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases National Health and Family Planning Commission, Xi'an, Shaanxi 710061, P.R. China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: X I
authors.initials: XI
authors.lastname: Wang
authors.affiliation: Wuqing People's Hospital of Tianjin, Tianjin 301700, P.R. China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Zhen
authors.affiliation: School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases National Health and Family Planning Commission, Xi'an, Shaanxi 710061, P.R. China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Su
authors.affiliation: School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases National Health and Family Planning Commission, Xi'an, Shaanxi 710061, P.R. China; Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Wuhong
authors.initials: W
authors.lastname: Tan
keywords: 20-hydroxyeicosatetraenoic acids; Keshan disease; arachidonic acid; dilated cardiomyopathy; epoxyeicosatrienoic acids