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Application of ZNF418 (zinc finger protein 418) to treatment of myocardial hypertrophy

A zinc finger protein and myocardial hypertrophy technology, which is applied in the field of preparation of drugs for the prevention, alleviation and/or treatment of myocardial hypertrophy, can solve the problems of no therapeutic drugs and schemes, complex pathogenesis of HCM, and unclear mechanism, and achieve inhibition Cardiac hypertrophy, anti-cardiac fibrosis, myocardial hypertrophy, and cardiac function protection effects

Inactive Publication Date: 2015-11-25
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 ZNF418 (zinc finger protein 418) to treatment of myocardial hypertrophy
  • Application of ZNF418 (zinc finger protein 418) to treatment of myocardial hypertrophy
  • Application of ZNF418 (zinc finger protein 418) to treatment of myocardial hypertrophy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0089] [Example 1] Expression of ZNF418 in the hearts of normal people and patients with cardiomyopathy

[0090] Normal human hearts (individuals donated by non-cardiac causes of death), hearts of patients with dilated cardiomyopathy (recipients replaced by patients undergoing heart transplantation, DCM) and SDS-PAGE-immunoblotting tests (Westernblot) were performed on proteins extracted from the hearts. ), combined with antibodies that specifically recognize ZNF418 protein and cardiomyocyte hypertrophy markers ANP (Millipore, AB2232) and Myh7 (santacruz, sc53090) to detect the expression of ZNF418 (ProSci, 26-559), GAPDH (Cell Signaling Technology, 2128 ) as an internal reference. Test results such as figure 1 As shown, the expression of cardiomyocyte hypertrophy markers ANP and Myh7 in the hearts of patients with dilated cardiomyopathy was significantly up-regulated, and the expression of ZNF418 was significantly down-regulated ( figure 1 );.

Embodiment 2

[0091] [Example 2] Expression of ZNF418 in wild-type mouse Sham group and AB operation 4W, 8W hearts

[0092] 1. The myocardial hypertrophy model adopts aortic arch coarctation surgery, and the operation process of the model is as follows:

[0093] 1.1 Preoperative preparation

[0094] (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).

[0095] (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

[0105] [Example 3] The effect of ZNF418 interference (AdshZNF418) and overexpression (AdZNF418) adenovirus on the expression of ZNF418 in AngII-stimulated primary cardiomyocytes

[0106] 1. Primary neonatal SD rat cardiomyocyte culture

[0107] Sprague-Dawley neonatal rat cardiomyocytes were isolated and cultured for 1 day, and the medium was changed after 48 hours of primary cardiomyocytes.

[0108] 2. Effect of ZNF418 interference (AdshZNF418) and overexpression (AdZNF418) adenovirus on AngII-induced cardiomyocyte hypertrophy model

[0109] AdshRNA (adenovirus containing shRNA (silencing RNA), used as a control), AdshZNF418 (adenovirus containing shRNA-ZNF418 (silencing RNA-ZNF418 fusion protein)), AdGFP (adenovirus containing GFP (green fluorescent protein), used as control) and AdZNF418 (adenovirus containing GFP-ZNF418 green fluorescent protein-ZNF418 fusion protein) adenovirus 10MOIs respectively infected primary cardiomyocytes cultured for 3 days, and after 12 hours we...

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Abstract

The invention discloses an application of ZNF418 (zinc finger protein 418) to protection of cardiac functions, resistance to cardiac fibrosis and / or prevention, relief and / or treatment of myocardial hypertrophy, and belongs to the application field of genes. In a myocardial hypertrophy model, the expression of the ZNF418 is ensured to be significantly lower than that of a normal group; myocardial hypertrophy and fibrosis are significantly promoted and cardiac functions are deteriorated by inhibiting expression of the ZNF418, and the myocardial hypertrophy and fibrosis are significantly inhibited and the cardiac functions are protected by promoting overexpression of the ZNF418. The ZNF418 can be used as a drug target and used for screening of drugs for protecting the cardiac functions, resisting the cardiac fibrosis and / or preventing, relieving and / or treating the myocardial hypertrophy; the ZNF418 can be used as a target gene for gene therapy and used for designing and preparing drugs and / or biological reagents for protecting the cardiac functions, resisting the myocardial hypertrophy and / or preventing, relieving and / or treating the myocardial hypertrophy, and a new and effective way is provided for treatment of the 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 418 (ZNF418) in the treatment of cardiac hypertrophy, specifically the application in the preparation of drugs for preventing, alleviating and / or treating myocardial hypertrophy. Background technique [0002] Hypertrophic cardiomyopathy (HCM) is one of the main risk factors for heart failure. With the presence of hemodynamic load and continuous stress of neurohormones, physiological hypertrophy develops into pathological myocardial hypertrophy, which eventually leads to abnormal heart rate. Qi, heart failure, sudden death [1,2,3]. A variety of factors can lead to myocardial hypertrophy, such as pressure load, phenylephrine (PE), angiotensin II (AngII), etc., which eventually lead to enlargement of cardiomyocytes, increased collagen synthesis, and aggravated perivascular and interstitial fibrosis The corresponding ph...

Claims

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Application Information

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IPC IPC(8): A61K38/17C12Q1/68A61P9/00A61P9/04
Inventor 李红良李俊明潘黎明
Owner WUHAN UNIV
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