Application of EETs, sEH and sEH inhibitors in chronic heart failure

A chronic heart failure and inhibitor technology, applied in EETs, sEH inhibitors in chronic heart failure, sEH field, can solve problems such as insufficient risk assessment, difficulty in diagnosis and treatment of chronic heart failure, and achieve enhanced diagnosis and follow-up The effect of treatment, improving efficiency and accuracy, great application value

Active Publication Date: 2019-08-23
TONGJI HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI TECH
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The present invention aims at the difficulties in the diagnosis and treatment of chronic heart failure and insufficient risk assessment in the prior art, discovers two new biomarkers-EETs and sEH, and confirms their correlation with the onset of chronic heart failure, and their As a drug target in the prevention, alleviation and / or improvement of chronic heart failure; therefore, the detection of EETs and sEH levels through kits can be used to predict and assist in the diagnosis of chronic heart failure or evaluate the prognosis of chronic heart failure, and control the level of EETs through drugs , for more intensive diagnosis and follow-up treatment of the disease, which has great clinical application value

Method used

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  • Application of EETs, sEH and sEH inhibitors in chronic heart failure
  • Application of EETs, sEH and sEH inhibitors in chronic heart failure
  • Application of EETs, sEH and sEH inhibitors in chronic heart failure

Examples

Experimental program
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Effect test

Embodiment 1

[0038] EETs content decreased and sEH activity increased in peripheral blood of patients with chronic heart failure

[0039]Study population and study design: From January 2008 to March 2017, two medical centers (Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology in Wuhan City, Hubei Province, and the Second Affiliated Hospital of Hebei Medical University in Shijiazhuang, Hebei Province) were continuously included. Hospitalized patients with chronic heart failure. Inclusion criteria include: age greater than 18 years old, heart failure NYHA classification II-IV. The diagnosis of heart failure is determined on the basis of physical examination, laboratory examination, and echocardiography according to the diagnostic criteria and steps of ACC / AHA. Exclusion criteria include: heart failure caused by severe valvular disease; patients with life-threatening complications such as severe liver dysfunction and renal dysfunction; survi...

Embodiment 2

[0044] Increased expression of sEH protein in myocardial tissue of patients with chronic heart failure

[0045] Study population and study design: From January 2010 to March 2017, hospitalized patients who underwent heart transplantation for chronic heart failure were enrolled in Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province. Inclusion criteria include: age greater than 18 years old, heart failure NYHA class IV. The diagnosis of heart failure is determined on the basis of physical examination, laboratory examination, and echocardiography according to the diagnostic criteria and steps of ACC / AHA. Exclusion criteria include: patients with life-threatening complications such as severe liver dysfunction and renal dysfunction; survival time of patients with malignant tumors less than 1 year. Failing heart tissue from transplant recipients was immediately frozen in liquid nitrogen after removal from the pat...

Embodiment 3

[0049] PE can induce the increase of sEH activity in cardiomyocytes and damage the function of cardiomyocytes, while AUDA can inhibit these effects

[0050] Sources of biological materials: human cardiomyocyte cell line AC16 was purchased from ATCC in the United States, PE was purchased from Sigma Company, and AUDA was purchased from Cayman Company.

[0051] Cell intervention method: PE is dissolved in sterilized deionized water, the working concentration is 100uM; AUDA is dissolved in DMSO solvent, the working concentration is 1mM; the intervention time is 24 hours.

[0052] sEH activity detection: ELISA detection kit (BIOTARGET 14,15-EET / DHET ELISA KIT) from Detroit R&D Company was used.

[0053] Ventricular remodeling biomarker mRNA detection: Total RNA was extracted using Invitrogen's Trizol reagent, then cDNA was obtained using TAKARA's reverse transcription kit, and finally specific primers were used to amplify the mRNA content of related genes.

[0054] Apoptosis detec...

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Abstract

The invention discloses an application of EETs, sEH and sEH inhibitors in chronic heart failure, and belongs to the field of diagnosis, prevention and treatment of cardiovascular diseases. Two novel biomarkers-EETs and sEH are found, the effect of the biomarkers-EETs and sEH in the diagnosis of biomarkers in the chronic heart failure is proved as well as the effect of the biomarkers-EETs and sEH as a drug target in preventing, alleviating and / or improving the chronic heart failure; therefore, by detecting the EETs and sEH levels, the EETs and the sEH can predict and assist in the diagnosis ofthe chronic heart failure or assess the prognosis of the chronic heart failure; and meanwhile, the EETs level is controlled through drugs, diseases can be subjected to more intensive diagnosis and follow-up treatment, thus the EETs and the sEH haves huge application value in clinical practice.

Description

technical field [0001] The invention relates to the fields of diagnosis, prevention and treatment of cardiovascular diseases, in particular to the application of EETs, sEH and sEH inhibitors in chronic heart failure. Background technique [0002] Heart failure is a clinical syndrome in which different cardiovascular system diseases lead to myocardial damage and develops to the end stage. Its main pathophysiological features are impaired ventricular filling and ejection ability, which eventually leads to low ventricular pumping function. Its prognosis is poor and mortality is high. It is one of the most important causes that threaten human health and increase medical burden. It is especially important for China with an aging population. It is currently the main cause of death for Chinese people, accounting for more than 40% of the total death. One of the leading causes of health and increased healthcare burden. However, in the past 20 years, there has been no significant pro...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/573G01N33/68G01N33/50G01N30/02G01N30/72G01N30/88A61K45/00A61K31/20A61P9/04
CPCA61K31/20A61K45/00A61P9/04G01N30/02G01N30/72G01N30/88G01N33/5061G01N33/573G01N33/6893G01N2030/8813G01N2800/321G01N2800/324G01N2800/325
Inventor 汪道文陈琛宋紫萍
Owner TONGJI HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI TECH
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