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Polynucleotide and application of same in diagnosis and treatment of cardiovascular diseases

A polynucleotide and cardiovascular technology, applied in the field of peptides/proteins, can solve the problems of unclear function of NCoR1, gene therapy of no disease, etc., and achieve the effect of improving myocardial hypertrophy

Inactive Publication Date: 2019-05-28
SHANGHAI NINTH PEOPLES HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the function of NCoR1 in cardiovascular cells and many cardiovascular diseases is still unclear, and there are no reports of using NCoR1 for gene therapy of diseases

Method used

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  • Polynucleotide and application of same in diagnosis and treatment of cardiovascular diseases
  • Polynucleotide and application of same in diagnosis and treatment of cardiovascular diseases
  • Polynucleotide and application of same in diagnosis and treatment of cardiovascular diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0093] Example 1: Effect of RIDs core fragments in NCoR1 or NCoR1 on improving cardiovascular diseases such as myocardial hypertrophy and impaired cardiac function caused by pressure overload

[0094] Using small interfering RNA technology to knock down NCoR1, and then observe the effect on cardiomyocyte hypertrophy induced by phenylephrine. After immunofluorescence staining and quantitative analysis of cardiomyocytes, it was found that knocking down NCoR1 significantly promoted cardiomyocyte hypertrophy induced by phenylephrine ( figure 1 ).

[0095] Cardiomyocyte-specific NCoR1 knockout mice were obtained by crossing floxed NCoR1 mice with αMHC-Cre mice. After the mice were sacrificed, the ratio of ventricular weight to body weight (VW / BW, mg / g) was used to evaluate the situation of myocardial hypertrophy. The ventricle was dissected and the ventricular section near the base of the heart was fixed in 4% paraformaldehyde for histological analysis, and the left ventricle was...

Embodiment 2

[0100] Example 2: Verification of the correlation between the expression level of myocardial NCoR1 protein and the occurrence of cardiac hypertrophy diseases

[0101] Heart tissue from patients with hypertrophic cardiomyopathy and mouse models of cardiac hypertrophy were collected, total protein was extracted using RIPA buffer containing protease inhibitors, the samples were separated by SDS-PAGE, and then transferred to PVDF membrane. After incubation with primary and secondary antibodies, the protein expression level of NCoR1 in hypertrophic myocardial tissue was detected, and the protein expression was visualized using ECL Western blotting substrate and quantified using Image J software. The results showed that the expression of myocardial NCoR1 protein in patients with cardiac hypertrophy was significantly higher than that in healthy controls ( Figure 9 ). In the mouse myocardial hypertrophy model caused by pressure overload, the protein level of NCoR1 in myocardial tiss...

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Abstract

The invention discloses polynucleotide having the sequence as shown in SEQ ID No. 1. The polynucleotide or a vector provided by the invention carries NCoR1 or an RIDs core fragment in the NCoR1, and can significantly alleviate the cardiovascular diseases, such as cardiac hypertrophy and cardiac dysfunction, caused by pressure overload after cell transduction; it is verified that the expression ofthe NCoR1 in myocardial tissues of patients and mice suffering from the cardiac hypertrophy is increased and the NCoR1 can be used as a biomarker for diagnosis of the cardiac hypertrophy.

Description

technical field [0001] The present invention relates to a polynucleotide and its expressed polypeptide / protein, in particular to a polypeptide / protein utilizing nuclear receptor corepressor 1 (NCoR1) and its partial polynucleotide sequence and its expression. Diagnosis and treatment of cardiovascular diseases. Background technique [0002] Nuclear receptor co-repressor 1 (NCoR1) is a transcriptional cofactor that normally functions with transcription factors and chromatin modifying enzymes and is involved in regulating the expression of a large number of genes. Existing animal experiment data show that NCoR1 plays an important role in metabolic diseases such as obesity and type 2 diabetes. However, the function of NCoR1 in cardiovascular cells and many cardiovascular diseases is still unclear, and there is no report on the use of NCoR1 in gene therapy for diseases. Contents of the invention [0003] One object of the present invention is to provide a polynucleotide that ...

Claims

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Application Information

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IPC IPC(8): C12N15/12A61K31/711A61P9/00A61P9/04G16B30/10G16B25/10G16H50/20
Inventor 段胜仲李超孙雪楠陈柏延曾梦茹柳燕
Owner SHANGHAI NINTH PEOPLES HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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