Function and application of activin receptor-like kinase7 (ALK7) in treatment of cardiac hypertrophy

A technology of ALK7, 1. The application of ALK7 in the preparation of drugs for the prevention, alleviation and/or treatment of cardiac hypertrophy, the function and application field of activin receptor-like kinase 7 (ALK7) in the treatment of cardiac hypertrophy, can solve There is no effective way to reduce cardiovascular events, cardiovascular disease morbidity and mortality, etc., to achieve the effect of inhibiting myocardial hypertrophy and protecting heart function

Active Publication Date: 2014-10-29
武汉惠康基因科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The morbidity and mortality of cardiovascular diseases continue to increase worldwide, and despite advances in treatment methods, there is still no effective way to reduce the occurrence of cardiovascular events

Method used

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  • Function and application of activin receptor-like kinase7 (ALK7) in treatment of cardiac hypertrophy
  • Function and application of activin receptor-like kinase7 (ALK7) in treatment of cardiac hypertrophy
  • Function and application of activin receptor-like kinase7 (ALK7) in treatment of cardiac hypertrophy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] Example 1 Expression of ALK7 in the hearts of normal people and patients with hypertrophic cardiomyopathy

[0052]SDS-PAGE-Western blot was performed on proteins extracted from the hearts of normal human hearts (individuals donated by non-cardiac causes of death) and hearts of patients with hypertrophic cardiomyopathy (recipients replaced by patients undergoing heart transplantation). Combined with antibodies that specifically recognize ALK7 (Abgent, AP7102b) protein and cardiomyocyte hypertrophy markers ANP (Millipore, AB2232), Myh7 (santa cruz, sc53090) to detect the expression of ALK7, GAPDH (Cell Signaling Technology, 2118) Do internal reference. Test results such as figure 1 As shown, compared with normal human hearts, the expression of cardiomyocyte hypertrophy markers ANP and Myh7 in patients with hypertrophic cardiomyopathy was significantly up-regulated, and the expression of ALK7 was significantly down-regulated.

Embodiment 2

[0053] Example 2 Expression of ALK7 in wild-type mouse Sham group and AB operation 4W, 8W hearts

[0054] 1. The myocardial hypertrophy model adopts aortic arch constriction surgery, and the operation process of the model is as follows:

[0055] 1.1 Preoperative preparation

[0056] (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).

[0057] (2) Preparation of the operation area: the skin of the left chest, left chest and armpit of the left forelimb of the mouse was remo...

Embodiment 3

[0066] Example 3 Effect of ALK7 interference (Adsh ALK7) and overexpression (Ad ALK7) adenovirus on ALK7 expression in AngⅡ-stimulated primary cardiomyocytes

[0067] 1. Primary neonatal SD rat cardiomyocyte culture

[0068] (1) Newborn 1-day Sprague-Dawley suckling mice were disinfected with 75% alcohol below the neck, and the heart was removed with ophthalmic scissors and micro forceps, and placed in a glass dish filled with 10mL DMEM / F12 solution. Take another one and repeat the above process.

[0069] (2) Wash the heart with DMEM / F12 medium, and cut the heart into 1-2mm 3 fragments. Transfer to a serum bottle with a rotor, suck off DMEM / F12, and add trypsin digestion solution. Rotate at 120r / min, digest for 15min, rest for a few seconds, and discard the supernatant.

[0070] (3) Add trypsin digestion solution, the speed is 120r / min, and digest for 15min. Stand still for a few seconds, aspirate the supernatant, terminate the digestion with DMEM / F12 medium with 20% calf...

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Abstract

The invention discloses a function and application of activin receptor-like kinase7 (ALK7) in treatment of a cardiac hypertrophy disease. According to the invention, the relationship between an ALK7 gene and the cardiac hypertrophy is determined: when the cardiac hypertrophy occurs, the expression of ALK7 is obviously reduced; the interference of ALK7 and over-expressed adenovirus are respectively used for promoting and inhibiting cardiomyocyte hypertrophy; ALK7 gene knockout has the effect of remarkably enhancing the activation of MEK1 / 2 / ERK1 / 2 and Smad2 / Samd3 signal channels so that the cardiac hypertrophy and fibrosis are promoted and the heart function is worsened; over-expression of the ALK7 gene has the effect of remarkably reducing the activation of MEK1 / 2 / ERK1 / 2 and Smad2 / Samd3 signal channels so that the cardiac hypertrophy and fibrosis are inhibited and the heart function is improved. Therefore, the ALK7 gene can be used as a target gene in gene therapy and can be used for preparing a medicine for protecting the heart function and / or preventing, relieving and / or treating the cardiac hypertrophy, thus providing a new way for treating the cardiac hypertrophy.

Description

technical field [0001] The present invention belongs to the field of gene function and application, and in particular relates to the function and application of activin receptor-like kinase 7 (ALK7) in the treatment of cardiac hypertrophy, specifically in the preparation of drugs for preventing, alleviating and / or treating cardiac hypertrophy application. Background technique [0002] According to the report of the World Health Organization, cardiovascular disease has become one of the global chronic non-communicable diseases that threaten human life and health. A variety of cardiovascular diseases, including hypertension, atherosclerosis, valvular heart disease, and cardiomyopathy, progress to heart failure, which is the leading cause of hospitalization and death for most patients. Myocardial hypertrophy refers to the increase in heart weight and volume in order to adapt to the increase in heart work under the influence of genetics, environment, and various physiological ...

Claims

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Application Information

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IPC IPC(8): A61K38/45A61P9/04A61P9/00
Inventor 李红良蒋丁胜蒋曦张晓东
Owner 武汉惠康基因科技有限公司
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