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Application of zinc finger protein 436 (ZNF 436) to treatment of myocardial hypertrophy

A technology of zinc finger protein and cardiac hypertrophy, applied in the application of drugs for alleviating and/or treating cardiac hypertrophy, preparation of prevention, application field of zinc finger protein 436 (ZNF436) in the treatment of cardiac hypertrophy, which can solve the problem of no therapeutic drugs and In order to achieve the effects of inhibiting cardiac hypertrophy, anti-cardiac fibrosis, cardiac hypertrophy and protecting cardiac function

Inactive Publication Date: 2015-12-09
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

So far, many studies have shown that the pathogenesis of HCM is complicated, but its mechanism is still not very clear, and there is no special and effective treatment drug and program in clinical practice.

Method used

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  • Application of zinc finger protein 436 (ZNF 436) to treatment of myocardial hypertrophy
  • Application of zinc finger protein 436 (ZNF 436) to treatment of myocardial hypertrophy
  • Application of zinc finger protein 436 (ZNF 436) to treatment of myocardial hypertrophy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0083] [Example 1] Expression of ZNF436 in the hearts of normal people and patients with dilated heart disease

[0084] Normal human hearts (individuals donated by non-cardiac causes of death) and hearts of patients with dilated heart disease (recipients replaced by patients undergoing heart transplantation) were selected, and SDS-PAGE-Western blot test (Western blot) was performed on the proteins extracted from the hearts, and the binding specificity Antibodies recognizing ZNF436 protein and cardiomyocyte hypertrophy markers ANP (Millipore, AB2232) and β-MHC (santacruz, sc53090) were detected to measure the expression of ZNF436 (ATLAS, HPA043817), and GAPDH (Cell Signaling Technology, 2128) was used as an internal reference. Test results such as figure 1 As shown in A, the expression of cardiomyocyte hypertrophy markers ANP and β-MHC in the heart of patients with dilated cardiomyopathy was significantly up-regulated, and the expression of ZNF436 was significantly up-regulated...

Embodiment 2

[0085] [Example 2] Expression of ZNF436 in wild-type mouse Sham group and AB operation 4W, 8W hearts

[0086] 1. The myocardial hypertrophy model adopts aortic arch coarctation surgery, and the operation process of the model is as follows:

[0087] 1.1 Preoperative preparation

[0088] (1) Anesthesia: First weigh the mice, calculate the required amount of anesthetic (3% pentobarbital sodium) according to 90 mg / kg body weight, inject intraperitoneally, and record the injection time point. There is no obvious reaction between tail and toe pinching and the mouse is in good condition. This is the standard for successful anesthesia (generally there is no obvious reaction about 10 minutes after injection, and the mouse has a reaction to pinch toe about 50 minutes after anesthesia, and about 30 minutes after anesthesia is the best operation time).

[0089] (2) Preparation of the operation area: the skin of the left chest, left chest and armpit of the left forelimb of the mouse was r...

Embodiment 3

[0099] [Example 3] Expression of ZNF436 in cardiomyocytes stimulated by control group (PBS) or angiotensin II (AngII) or phenylephrine (PE)

[0100] Isolate and culture newborn 1-day Sprague-Dawley neonatal rat cardiomyocytes, culture the primary cardiomyocytes for 48 hours, change the medium, add serum-free DMEM / F12 starved cardiomyocytes for 12 hours to synchronize the cells, and give PBS and angiotensin II (AngII respectively) , 1 μM), phenylephrine (PE, 1 μM) stimulation for 48 hours, SDS-PAGE-immunoblotting test (Western blot) was performed on the protein extracted from cardiomyocytes, combined with specific recognition of ZNF436 protein and cardiomyocyte hypertrophy markers ANP, β-MHC The antibody was detected, and the expression of ZNF436 was determined, and the detection results were as follows: figure 1 C shown. The expressions of ANP, β-MHC and ZNF436 were significantly up-regulated in cardiomyocytes stimulated by angiotensin II (AngII) or phenylephrine (PE).

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Abstract

The invention discloses an application of zinc finger protein 436 (ZNF 436) to protection of the cardiac function, resistance to myocardial fibrosis and / or prevention, relief and treatment of myocardial hypertrophy, and belongs to the field of genetic application. According to the application, it is determined that ZNF 436 expression is lowered obviously compared with a normal group in a myocardial hypertrophy generation model; through inhibition of the ZNF 436 expression, the myocardial hypertrophy and fibrosis are promoted remarkably, and the cardiac function is deteriorated; by promoting ZNF 436 overexpression, the myocardial hypertrophy and fibrosis are inhibited obviously, and the cardiac function is protected. The ZNF 436 can be used as a drug target, and is used in drugs for screening protection of the cardiac function, resistance to myocardial fibrosis and / or prevention, relief and treatment of myocardial hypertrophy. The ZNF 436 can be used as a target gene used in gene therapy, and is used for designing and preparing drugs and / or biological reagents for protection of the cardiac function, resistance to myocardial fibrosis and / or prevention, relief and treatment of myocardial hypertrophy. A new effective path is provided for treatment of myocardial hypertrophy.

Description

technical field [0001] The invention belongs to the field of gene function and application, and particularly relates to the application of a zinc finger protein 436 (ZNF436) in the treatment of cardiac hypertrophy, specifically the application in the preparation of drugs for preventing, alleviating and / or treating cardiac hypertrophy. Background technique [0002] Myocardial hypertrophy is the compensatory response of the myocardium to long-term biomechanical pressure or increased volume load, which is commonly seen in cardiovascular diseases such as hypertension and aortic stenosis. Increased and other characteristics [1-3]. Hypertension and senile degenerative aortic valve disease are on the rise year by year in our country. Cardiac hypertrophy and the incidence of hypertension and heart disease caused by hypertension and other diseases also increase thereupon. Although myocardial hypertrophy can initially increase myocardial cells and strengthen myocardial contractility...

Claims

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Application Information

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IPC IPC(8): A61K38/17A61K45/00A61P9/00C12Q1/68
Inventor 李红良唐艳红张晓晶王丕晓
Owner WUHAN UNIV
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