Application of FKBP11 gene in prevention and treatment of aortic dissection

A technology of aortic dissection and gene, applied in gene therapy, medical preparations containing active ingredients, screening of compounds, etc., to achieve the effects of inhibiting migration, inhibiting degradation, and reducing expression

Active Publication Date: 2018-03-23
TONGJI HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But so far, there is no report on the role of FKBP11 in cardiovascular diseases, especially aortic dissection

Method used

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  • Application of FKBP11 gene in prevention and treatment of aortic dissection
  • Application of FKBP11 gene in prevention and treatment of aortic dissection
  • Application of FKBP11 gene in prevention and treatment of aortic dissection

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0058] Example 1: Discovery of the relationship between FKBP11 gene and acute aortic dissection:

[0059] The applicant used the whole aortic tissue RNA of patients with aortic dissection to obtain the transcriptome database by analyzing the Illumina HumanHT-12V4.0 gene chip (Illumina Inc., San Diego, CA, USA), and constructed a differential expression profile matrix using the WGCNA method Data, after removing outlier samples, carried out gene module analysis, gene enrichment analysis, hub gene screening, and the screened genes related to the occurrence and development of aortic dissection were verified by independent samples and isolated cell experiments, and FKBP11 was established as the target target gene.

[0060] The applicant used clinical samples of aortic tissue from patients with acute active dissection and normal aortic tissue samples as a control to study the relationship between FKBP11 gene and acute aortic dissection through Western Blot and immunohistochemical ex...

Embodiment 2

[0064] Example 2: FKBP11 gene causes the mechanism of action of aortic dissection disease

[0065] Endothelial cell damage is the initiating link of various cardiovascular diseases. When endothelial cells are stimulated by the outside world, the highly expressed FKBP11 of endothelial cells activates the NF-KB pathway by promoting p-P65 to enter the nucleus, increasing the expression of inflammatory factors in endothelial cells. Promoting the migration and differentiation of monocytes in the circulation causes macrophages to enter the aortic media through activated endothelial cells, and the aggregated macrophages will recruit more by secreting inflammatory factors (such as IL-6, MCP-1, etc.) Adhesion of inflammatory cells to endothelial cells and migration of tunica media aggravate the local infiltration of inflammatory cells. At the same time, macrophages will secrete a large amount of matrix metalloproteinases (MMPs) and proteases that can degrade structural proteins such as...

Embodiment 3

[0066] Example 3: FKBP11 gene knockdown significantly reduces the expression of pro-inflammatory factors and the migration of monocyte-macrophages

[0067] The applicant induced EA.hy926 endothelial cells with angiotensin-converting enzyme II (Ang II) to simulate the occurrence of aortic dissection in vitro.

[0068] 1. Screening and verification of effective FKBP11SiRNA:

[0069] (1) Cell culture: THP-1 cells ( tib-202 TM ) and EA.hy926 cells (Manassas, VA), cultured in RPMI 1640 (Gibco, CA, USA) containing 10% fetal bovine serum (Sigma-Aldrich, St.Louis, MO), containing 10mM HEPEs, 0.1mM MEM non Essential amino acids, 1 mM sodium pyruvate, and 100 nM penicillin / streptomycin (Life Technologies), maintained at 5% CO 2 , in a 37 °C cell culture incubator. Synthetic FKBP11-siRNA was purchased from Ruibo (Guangzhou, China), and the specific operation of transfecting cells was according to the manufacturer's protocol. Three artificially synthesized FKBP11-siRNAs, as follows...

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Abstract

The invention belongs to the fields of gene functions and applications, and specifically discloses an application of an FKBP11 gene in prevention and treatment of aortic dissection. In-vitro cell experiments show that vascular endothelial cell SiRNA-mediated FKBP11 gene silencing can inhibit activation of an NF-kB signal pathway, the expression of a proinflammatory cytokine is decreased, and migration of macrophage to an aortic middle layer is inhibited, so that the degradation of a middle-layer substrate is inhibited, and results show that the FKBP11 inhibitor can prevent and treat occurrenceof aortic dissection, and provides theoretical basis and clinical basis for new targets and new strategies for prevention, relieving and / or treatment of aortic dissection.

Description

technical field [0001] The present invention belongs to the field of gene function and application, and specifically relates to the application of FKBP11 gene in the prevention and treatment of aortic dissection, and also relates to the application of FKBP11 gene as a drug target in the screening of drugs for the treatment of aortic dissection, and the use of FKBP11 gene inhibitors in the preparation and treatment of aortic dissection. Drug application in aortic dissection disease. Background technique [0002] Aortic dissection (AD) refers to the sudden tearing of the aortic intima caused by various reasons, circulating blood enters the media of the vessel wall and causes its stratification, and gradually expands in the media of the aorta with the pressure of the blood flow Form a sandwich. Acute onset, sudden severe chest pain, shock and involvement of corresponding aortic branch vessels lead to acute ischemia of organs are the characteristics of the disease. In my count...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6883G01N33/573A61K45/00A61K48/00A61K31/7088A61P9/10
CPCA61K31/7088A61K45/00A61K48/005C12Q1/6883C12Q2600/136C12Q2600/158G01N33/573G01N2333/99G01N2500/04
Inventor 曾和松王洪杰王涛
Owner TONGJI HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI TECH
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