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Application of ABRA in preparation of medicine for improving myocardial function of dilated cardiomyopathy

A technology for dilated cardiomyopathy and cardiac function, applied in the field of biomedicine, can solve problems such as affecting the patient's ability to work, sudden death, etc.

Pending Publication Date: 2020-10-09
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the clinical manifestations are different, both DCM and HCM will greatly affect the patient's ability to work, and in severe cases lead to sudden death

Method used

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  • Application of ABRA in preparation of medicine for improving myocardial function of dilated cardiomyopathy
  • Application of ABRA in preparation of medicine for improving myocardial function of dilated cardiomyopathy
  • Application of ABRA in preparation of medicine for improving myocardial function of dilated cardiomyopathy

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Experimental program
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Effect test

Embodiment 1

[0034] The ΔK210 and ΔE160 mutations were introduced into the genome of human embryonic stem cells (hESCs, human embryonic stem cells) by TALEN gene editing and homologous recombination technology to establish human embryonic stem cell lines with ΔK210 and ΔE160 mutations ( figure 2 ), further directional induction to the myocardium to differentiate into human pluripotent stem cell-derived cardiomyocytes (hESC-CMs) with ΔK210 and ΔE160 mutations.

Embodiment 2

[0036] Immunofluorescent staining and transmission electron microscopy were performed on the differentiated wild-type (WT / WT) and mutant hESC-CMs to observe the cell morphology changes. Compared with the wild type, the sarcomeres of cardiomyocytes with the ΔK210 mutation were disordered Even structurally incomplete, heterozygous cardiomyocytes with the ΔE160 mutation had thicker sarcomeres ( image 3 ).

Embodiment 3

[0038]The electrophysiological properties of cardiomyocytes were detected by multi-electrode microarray (multi-electrodearray, MEA) and calcium transient detection, and the contractility of cardiomyocytes was measured to evaluate their functional changes, so as to verify the functions of ΔK210 and ΔE160 cardiomyocytes. Through detection, it was found that hESC-CMs with ΔK210 mutation had reduced contractility, with a disease phenotype similar to dilated cardiomyopathy, while hESC-CMs with ΔE160 mutation had increased contractility, with a similar disease phenotype to hypertrophic cardiomyopathy disease phenotype ( Figure 4 ), can serve as a good human cardiomyocyte model of disease.

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Abstract

The invention belongs to the field of biological medicines. The invention relates to a medicine for improving the cardiac function of dilated cardiomyopathy, in particular to a medicament for improving the myocardial cell function of family hereditary dilated cardiomyopathy and a method thereof. The overexpression ABRA gene can remarkably improve the myocardial cell morphology of delta K210 mutation and R141W mutation of troponin T and the cardiac function of the dilated cardiomyopathy with corresponding mutation. The invention provides an application of an ABRA gene in preparation of a medicine for improving myocardial functions, and further relates to a method for improving myocardial cell functions in vitro. The invention provides a new way and a method for improving the functions of myocardial cells, and particularly, ABRA has a remarkable effect of improving the forms and functions of the myocardial cells aiming at the dilated cardiomyopathy caused by deletion and point mutation on troponin T subunit, and can further improve the cardiac function of the dilated cardiomyopathy.

Description

technical field [0001] The invention relates to the field of biomedicine, and relates to a new application of ABRA gene, in particular to the application of ABRA in the preparation of drugs for improving myocardial function in dilated cardiomyopathy Background technique [0002] The study disclosed that the TNNT2-ΔK210 mutation is the deletion of the 210th lysine of the TNNT2 gene, and the conformational change caused by the deletion mutation on the troponin T subunit exposes the threonine residue and increases the phosphorylation level, which affects the The sarcomere structure reduces calcium ion sensitivity, which leads to the occurrence of dilated cardiomyopathy (DCM). DCM is a primary cardiomyopathy of unknown etiology characterized by left or right ventricle or bilateral ventricle enlargement, accompanied by ventricular systolic dysfunction, with or without congestive heart failure. Ventricular or atrial arrhythmias are common. The condition is progressively exacerba...

Claims

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Application Information

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IPC IPC(8): A61K31/713A61K48/00A61P9/04
CPCA61K48/005A61K31/713A61P9/04
Inventor 孙宁李宾詹永坤
Owner FUDAN UNIV
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