Application of hdac4 inhibitor in preparation of medicine for treating heart failure

A technology of heart failure and reagents, applied in the field of biomedicine, to achieve the effects of improving exercise endurance, improving mitochondrial structure and function, and improving glucose and lipid metabolism

Active Publication Date: 2020-10-16
ZHONGSHAN HOSPITAL FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0007] However, there is no report on the role of HDAC4-specific inhibitors in the preparation of heart failure after myocardial infarction

Method used

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  • Application of hdac4 inhibitor in preparation of medicine for treating heart failure
  • Application of hdac4 inhibitor in preparation of medicine for treating heart failure
  • Application of hdac4 inhibitor in preparation of medicine for treating heart failure

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] We established an animal model of heart failure after myocardial infarction in mice, and used a small animal treadmill for aerobic exercise intervention. Using PET / CT, echocardiography and molecular biology techniques to evaluate cardiac function, energy metabolism and related signaling molecules, it was found that aerobic exercise can improve cardiac function after infarction, increase exercise endurance, improve mitochondrial structure and function and glucose and lipid metabolism, and reduce Cardiac HDAC4 nuclear gene repression. The details are as follows: Acute myocardial infarction was caused by ligating the coronary arteries of mice, and the heart failure model after myocardial infarction was confirmed successfully by echocardiography one week later. After 4 weeks of aerobic exercise for mice with heart failure, the LVEF was improved compared with the control group, and the running distance and exercise tolerance were significantly increased. The transmission el...

Embodiment 2

[0060] 1. Experimental method

[0061] LMK235 was purchased from ApexBio, and the drug was dissolved in DMSO and diluted in saline. The heart failure model mice after myocardial infarction in the experimental group were injected intraperitoneally 5 times a week at a dose of 5 mg / kg, and the DMSO group was injected with the same concentration and dose of DMSO. Exercise tolerance and LVEF were measured according to the method described in Example 1. In addition, through small animal echocardiography, after controlling the heart rate within a reasonable range, determine the size of the FS value.

[0062] 2. Experimental results

[0063] The results showed that after 4 weeks of intraperitoneal injection of HDAC4 inhibitor LMK235, the running distance of mice was significantly improved ( Figure 8 ), LVEF and FS improved from baseline ( Figure 9 and Figure 10 ), indicating that HDAC4 inhibitors can effectively treat heart failure after myocardial infarction, and the improvemen...

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Abstract

The invention relates to application of HDAC4 inhibitor in preparing medicine for treating heart failure. According to the application, a heart failure animal model after a mouse is died of myocardialinfarction is established, aerobic exercise interference is carried out, cardiac function, energy metabolism and related signal molecules are assessed by using PET / CT, echocardiography and a molecular biological technique, it is found that the aerobic exercise can improve the cardiac function after infarction, increase exercise tolerance, improve mitochondrion structure function and glycolipid metabolism, and reduce the inhibiting effect of myocardium HDAC4 intra-nuclear genes, it is suggested that the DHAC4 is a molecular action target spot for the aerobic exercise to improve the cardiac function after infarction, medicine promoting the phosphorylation of the DHAC4 or reducing the expression of the DHAC4 can be developed, effect same as rehabilitation exercise can be achieved, complianceis improved, thereby improving symptoms, improving exercise tolerance, reducing case fatality rate, and the application has important clinical significance. The application further suggests that thephosphorylation level of the DHAC4 can serve as a marker for cardiac failure prognosis after myocardial infarction.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to the application of HDAC4 inhibitors in the preparation of medicines for treating heart failure. Background technique [0002] As a serious and terminal stage of various cardiovascular diseases, heart failure has a high incidence and poor prognosis, and has become one of the most important public health problems facing our country and the world. According to the latest statistics, the number of heart failure patients in my country is estimated to have exceeded 4.5 million, and the total hospitalization costs have increased rapidly, bringing huge social and economic burdens. Although the survival rate of patients with heart failure has been improved by drug therapy such as inhibiting neuroendocrine overactivation in the past 30 years, their quality of life and long-term prognosis are still poor, and the 1-year mortality rate is still as high as 17%. Existing treatment methods ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/00A61K31/166A61P9/04G01N33/573
CPCA61K31/166A61K45/00A61P9/04G01N33/5061G01N33/573G01N2800/324
Inventor 葛均波蒋昊孙爱军杨文龙贾代乐
Owner ZHONGSHAN HOSPITAL FUDAN UNIV
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