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Functions and application of growth arrest-specific proteins 6 (GAS6) to treating myocardial hypertrophy

A technology for myocardial hypertrophy and heart function, applied in gene therapy, microbial measurement/test, cardiovascular system diseases, etc., can solve problems such as malignant arrhythmia, coronary artery insufficiency, sudden death, etc., and achieve the effect of protecting heart function

Inactive Publication Date: 2015-12-30
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although myocardial hypertrophy can initially increase myocardial cells and strengthen myocardial contractility, which is a compensatory mechanism to maintain normal cardiac output, long-term continuous pressure or volume overload will cause myocardial remodeling, and at the same time due to myocardial Increased oxygen demand and relatively insufficient coronary blood supply lead to myocardial ischemia, myocardial cell apoptosis, and decompensation, leading to heart failure, malignant arrhythmia, and even sudden death[4,5]

Method used

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  • Functions and application of growth arrest-specific proteins 6 (GAS6) to treating myocardial hypertrophy
  • Functions and application of growth arrest-specific proteins 6 (GAS6) to treating myocardial hypertrophy
  • Functions and application of growth arrest-specific proteins 6 (GAS6) to treating myocardial hypertrophy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0082] The expression of embodiment 1GAS6 in the heart of normal people and patients with cardiomyopathy

[0083] Select normal human hearts (individuals donated by non-cardiac causes of death) and dilated cardiomyopathy patients’ hearts (recipients replaced by patients undergoing heart transplantation), and perform SDS-PAGE-Western blot test (Western blot) on proteins extracted from the hearts, combined with Antibodies that specifically recognize GAS6 protein and cardiomyocyte hypertrophy markers ANP (Millipore, AB2232) and β-MHC (santacruz, sc53090) were detected to measure the expression of GAS6 (santacruz, SC-1935), 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 β-MHC in the hearts of patients with dilated cardiomyopathy was significantly up-regulated, and the expression of GAS6 was significantly up-regulated ( figure 1 ).

Embodiment 2

[0084] Example 2 Expression of GAS6 in the heart of wild-type mouse sham operation group and cardiac hypertrophy model group

[0085] 1. Aortic arch constriction (AB) was used to establish a mouse model of myocardial hypertrophy. The model operation process:

[0086] 1.1 Preoperative preparation

[0087] (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).

[0088] (2) Preparation of the operation area: the skin of the left chest, left chest and armpit of the left forelimb...

Embodiment 3

[0099] Example 3 Expression of GAS6 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 and change the medium (see the following example 4 for the specific process of primary neonatal SD rat cardiomyocyte culture), add serum-free DMEM / F12 After starving cardiomyocytes for 12 hours to synchronize the cells, they were stimulated with PBS, angiotensin II (AngII, 1 μM) and phenylephrine (PE, 1 μM) for 48 hours, and SDS-PAGE-immunoblotting was performed on proteins extracted from cardiomyocytes ( Western blot), combined with antibodies that specifically recognize GAS6 protein and cardiomyocyte hypertrophy markers ANP and β-MHC, were used to detect the expression of GAS6, and GAPDH was used as an internal reference. Test results such as image 3 As shown, the expressions of ANP and β-MHC were significa...

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Abstract

The invention discloses functions and application of growth arrest-specific proteins 6 (GAS6) to treating myocardial hypertrophy, and belongs to the field of functions and application of genes. The functions and the application have the advantages that relationships between expression of the GAS6 and the myocardial hypertrophy are determined, and as shown by research results, expression of the GAS6 in models with the myocardial hypertrophy is obviously improved as compared with normal groups; myocardial hypertrophy and fibrosis can be obviously inhibited by means of inhibiting expression of the GAS6, and cardiac functions can be protected; the myocardial hypertrophy and fibrosis can be obviously promoted if over-expression of the GAS6 is promoted, and the cardiac functions can be deteriorated; the GAS6 can be used as a medicine target and can be used for screening medicine for protecting the cardiac functions, resisting the cardiac fibrosis and / or preventing, relieving and / or treating the myocardial hypertrophy; inhibitors of the GAS6 can be used for preparing medicine for protecting the cardiac functions, resisting the myocardial hypertrophy and / or preventing, relieving and / or treating the myocardial hypertrophy, and an effective novel way can be provided for treating the myocardial hypertrophy.

Description

technical field [0001] The invention belongs to the field of gene function and application, and in particular relates to the function and application of a growth arrest specific protein 6 (Growtharrest specific 6, GAS6) in the treatment of 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, which is a compensatory mechanism to maintain normal cardiac output, long-...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K48/00A61P9/00C12Q1/68
Inventor 李红良徐亚伟赵逸凡王丕晓张晓晶
Owner WUHAN UNIV
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