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Effects of epoxyeicosatrienoic acids on levels of eNOS phosphorylation and relevant signaling transduction pathways involved

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science{1.(Life sciences) 2005年第5期48卷 495-505页

作者： chen ruijuan1,{1., xiao xiao2 & wang daowen1 1. the institute of hypertension and department of internal medicine, tongji hospital, tongji medical college, huazhong university of science & technology, wuhan 430030, china 2. departments of Molecular Genetics and Biochemistry & Gene Therapy Center, university of Pittsburgh, Pittsburgh, PA, USA The institute of {1. and department of internal medicine Tongji Hospital Tongji Medical College Huazhong University of Science & Technology Wuhan 430030 China departments of Molecular Genetics and Biochemistry & Gene Therapy Center University of Pittsburgh Pittsburgh PA USA

Endothelial nitric oxide synthase (eNOS) is a key enzyme responsible for the regu-lation of vascular homeostasis. Many humor factors and mechanical forces can affect eNOS ac-tivity via phosphorylation modification but the mechanisms involved vary with stimuli applied. We have demonstrated that cytochrome P450 (CYP) epoxygenase-dependent metabolites of ara-chidonic acid, epoxyeicosatrienoic acids (EETs), can robustly up-regulate eNOS expression and its activity, however the relevant signaling pathways responsible for activity regulation are not well known. In this study, we explored the role of PI3 kinase (PI3K)/protein kinase B (Akt) sig-naling pathway in eNOS expression and its phosphorylation in response to EETs via direct addi-tion of EETs into cultured bovine aorta endothelial cells (BAECs) and recombinant adeno- asso-ciated virus-mediated transfection of CYP epoxygenase genes CYPF87V and CYP2C1. to pro-duce endogenous EETs followed by co-treatment with PI3K or Akt inhibitor. Results show that both exogenous and endogenous EETs could remarkably enhance eNOS expression and its phosphorylation at Ser1.79 and Thr497 residues; PI3K inhibitor LY294002 could inhibit EETs-induced increase in eNOS-Ser(P)1.79 but had no effect on the change of eNOS-Thr(P)497, while Akt inhibitor could attenuate the increase in phosphor-eNOS at both residues; both of the two inhibitors could block EETs-enhanced eNOS expression. These results lead to conclusions: (i) EETs-mediated regulation of eNOS activity may be related with the changes of phosphoryla-tion level at eNOS-Ser1.79 via PI3K/Akt and eNOS-Thr497 via Akt; (ii) PI3K/Akt signaling pathway is involved in the up-regulation of eNOS expression by EETs.

关键词： epoxyeicosatrienoic acids, endothelial nitric oxide synthase (eNOS), PI3 kinase, Protein kinase B (Akt), phosphorylation.

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Consensus on diagnostic criteria for Yin deficiency syndrome in hypertension:a modified Delphi study

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Journal of Traditional Chinese medicine 2023年第1期43卷 181-187页

作者： HE Yun HE Jing XU Xiangru LI Haixiao SHI Rongwei LIANG Junya ZHOU Ying ZHU Yao {1. xiaohu TANG Shuhua xiao Min ZHAN Libin PEI Yinghao jiang Weimin department of General {1. medicine Jiangsu Province Hospital of Chinese Medicine Affiliated to Hospital of Nanjing University of Traditional Chinese MedicineNanjing 210029China department of Hepatology Jiangsu Province Hospital of Chinese Medicine Affiliated to Hospital of Nanjing University of Traditional Chinese MedicineNanjing 210029China department of Emergency Longhua Hospital affiliated to Shanghai University of Traditional Chinese MedicineShanghai 200032China department of {1. of hypertension Jiangsu Province Hospital of Chinese Medicine Affiliated to Hospital of Nanjing University of Traditional Chinese MedicineNanjing 210029China department of Cardiology Jiangsu Province Hospital of Chinese Medicine Affiliated to Hospital of Nanjing University of Traditional Chinese MedicineNanjing 210029China department of Cardiology Dongzhimen Hospital Affiliated to Beijing University of Chinese MedicineBeijing 100700China School of Traditional Chinese medicine&School of Integrated Chinese and Western medicine Nanjing University of Chinese MedicineNanjing 210023China department of Intensive Care Unit Jiangsu Province Hospital of Chinese Medicine Affiliated to Hospital of Nanjing University of Traditional Chinese MedicineNanjing 210029China

OBJECTIVE:To reach consensus on the diagnostic criteria for Yin deficiency syndrome in hypertension(YDSH)patients by a modified Delphi ***:Our study was consistent with T/CACM *** methodology of RAND/UCLA appropriateness was used to develop consensus guidance statements.A nationwide panel of experienced clinical experts from 1. provinces was *** experts were all prominent in Traditional Chinese {1.(TCM)of cardiovascular *** consensus process consisted of two rounds of questionnaires and a final round of consultation to analyze the weight score of each ***,the data extraction process is carried out independently by third-party researchers(LIANG Junya,SUN Yang,and DU xiaona).When there is disagreement in all three rounds,the expert panel group(odd number)are invited to vote,and the one with more votes *** the questionnaires,participants were asked to rate the appropriateness of each syndrome item using a nine-point Likert *** consensus was defined as a panel median rating 1.3 or 7-9 without *** then the diagnostic criteria of YDSH were formed according to the weight score in the final ***:Twenty-eight experts(84.8%)participated in the first round,and thirty-one(93.9%)finished the second *** two rounds,the consensus of YDSH was reached on 1. items(25.6%),including symptoms,signs,and pulse ***-one experts(63.6%)completed the final round in which they used a grading system for each *** tongue with scanty fur had the highest weighting(22.8%),followed by heat in the palms and soles(20.1.).CONCLUSIONS:The consensus-based diagnostic criteria for YDSH,formed by a modified Delphi method,can be widely incorporated in TCM.A further clinical study will be conducted to analyze the diagnosis value and cut-off score of our YDSH criteria.

关键词： Yin deficiency syndrome hypertension consensus Delphi technique weight score

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