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Application of miRNA in treating cardiac hypertrophy

A kind of myocardial hypertrophy, CHO-PGEA- technology, applied in the field of medicine and biology, can solve problems such as poor clinical effect of drugs

Active Publication Date: 2020-05-22
BEIJING INST OF HEART LUNG & BLOOD VESSEL DISEASES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Although a large number of studies have shown that multiple signaling molecules are involved in cardiac hypertrophy, in addition to drugs such as ARB, multiple targets discovered based on animal experiments have not been successfully translated into clinical practice, which may be due to the huge differences between humans and animals. poor clinical effect

Method used

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  • Application of miRNA in treating cardiac hypertrophy
  • Application of miRNA in treating cardiac hypertrophy
  • Application of miRNA in treating cardiac hypertrophy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Example 1. Supplementation of hsa-miR-15a-5p / hsa-miR-16-5p (delivered by CHO-PEGA cation carrier) in vitro inhibits cardiac hypertrophy

[0037] The therapeutic effect of hsa-miR-15a-5p / hsa-miR-16-5p supplementation was tested.

[0038] Culture embryonic rat cardiomyocyte cell line (H9C2 cell line) in DMEM supplemented with 10% heat-inactivated fetal calf serum and antibiotics, culture embryonic rat cardiomyocyte cell line (H9C2 cell line) in a 24-well plate, and then add 20 μL CHO-PGEA-miRNA complex.

[0039] The preparation of the CHO-PGEA-miRNA complex can refer to the previous work of the applicant (such as CN201510377896.X, CN201910327563.4): mix the ingredients in the following table 3, shake for 5 seconds and then let stand for 30 minutes:

[0040] Table 3. Components of CHO-PGEA-miRNA complexes

[0041]

[0042] Cells were divided into negative control group and experimental group.

[0043] (1) Negative control group: 20 μL LCHO-PEGA-mirNC (no functional m...

Embodiment 2

[0058] Example 2. In vivo supplementation of hsa-miR-15a-5p / hsa-miR-16-5p (delivered by CHO-PEGA cation carrier) can completely inhibit TAC-induced cardiac hypertrophy and improve myocardial fatty acid oxidation

[0059] 1. Modeling steps of mouse TAC model:

[0060] (1) The mice were fixed under induction anesthesia. Maintain anesthesia with 1.5% isoflurane mixed gas through tracheal intubation;

[0061] (2) Disinfect the surgical area and prepare the skin for thoracotomy. Exposure of the thoracic aorta after thoracotomy;

[0062] (3) At the aortic arch, a 27G thin needle was placed parallel to the aortic arch and ligated together;

[0063] (4) After the ligation, draw out the fine needle to observe the condition of the mouse, and suture layer by layer after the condition is stable.

[0064] 2. Experimental grouping and scheme ( figure 2 A)

[0065] Select 15 wild mice and divide them into 3 groups, including:

[0066] (1) 5 mice in the blank control group: inject nor...

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Abstract

The invention relates to an application of miRNA in treating cardiac hypertrophy. Particularly, the miRNA is hsa-miR-15a-5p / hsa-miR-16-5p, and the nucleotide sequences of the miRNA are shown as SEQ IDNO.1 and SEQ ID NO.2. The cardiac hypertrophy refers to a pathophysiological process which is caused by overloading of a heart due to genetic factors, hypertension, myocardial infarction, valve diseases and the like and mainly takes thickening of ventricular muscles and narrowing of ventricular cavities as main characteristics. The invention also relates to an application of a complex loaded withthe hsa-miR-15a-5p / hsa-miR-16-5p in preparing a medicament for treating cardiac hypertrophy, wherein the complex is a CHO-PGEA-nucleic acid complex.

Description

technical field [0001] The invention belongs to the field of medical biotechnology, and specifically relates to the application of miRNA in the treatment of cardiac hypertrophy. Background technique [0002] Cardiovascular disease is still the leading cause of death, and its morbidity and mortality are increasing year by year. The heart responds to injury caused by myocardial infarction or sustained pressure overload through a variety of structural changes, commonly referred to as cardiac remodeling. At the cellular level, these changes include changes in cardiac hypertrophy, cardiomyocyte apoptosis, and expression of genes that regulate energy metabolism. Among them, myocardial hypertrophy is the main pathological process of hypertensive heart disease, hypertrophic cardiomyopathy and other cardiovascular diseases. Persistent myocardial hypertrophy can lead to heart failure and sudden death, which is an independent risk factor for cardiovascular disease. In general, myoca...

Claims

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Application Information

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IPC IPC(8): A61K31/7088A61P9/04
CPCA61K31/7088A61P9/04
Inventor 杜杰李玉琳许晨郝文静
Owner BEIJING INST OF HEART LUNG & BLOOD VESSEL DISEASES
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