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Application of reagent for inhibiting TERT expression in preparation of medicine for preventing or treating thoracic aortic aneurysm

A technology of thoracic aorta and reagents, which can be used in drug combinations, antineoplastic drugs, pharmaceutical formulations, etc., can solve the problems of no early diagnosis method of TAA, hidden onset, thoracic aortic dissection or aneurysm rupture, etc.

Active Publication Date: 2022-03-18
中国人民解放军海军军医大学第一附属医院
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Compared with other common cardiovascular diseases, although its incidence rate is low, due to its insidious onset, it is mostly asymptomatic in the early stage. As the disease progresses, thoracic aortic dissection or aneurysm rupture may occur and be life-threatening
At present, there is no early diagnosis method and effective preventive drug for TAA

Method used

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  • Application of reagent for inhibiting TERT expression in preparation of medicine for preventing or treating thoracic aortic aneurysm
  • Application of reagent for inhibiting TERT expression in preparation of medicine for preventing or treating thoracic aortic aneurysm
  • Application of reagent for inhibiting TERT expression in preparation of medicine for preventing or treating thoracic aortic aneurysm

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0056] Example 1: Collection of specimens from patients with thoracic aortic aneurysm and expression level of TERT

[0057] From December 2018 to December 2019, 22 cases of thoracic aortic tissue were obtained from intraoperative resected blood vessel specimens of patients undergoing surgery for thoracic aortic aneurysm in the Department of Thoracic and Cardiovascular Surgery of Changhai Hospital, and 10 cases of normal control group were obtained from organ donations By. The samples were collected and stored in liquid nitrogen. 1cm-sized tissues were fixed with 4% paraformaldehyde, embedded in wax blocks, histochemical staining and immunohistochemical staining were performed, and tissue proteins were extracted for Western blot. HE staining showed that compared with the normal thoracic aorta, the cells in TTA tissue were arranged disorderly and their polarity was disordered ( figure 1 A). VB staining showed that the blue-green elastic fiber sheets in TAA were broken and dest...

Embodiment 2

[0059] Example 2: Establishment and verification of thoracic aortic aneurysm mouse model

[0060] Forty-five C57BL / 6 adult male mice weighing 16-18 g were selected, and they were adaptively fed for 1 week with standard feed. Afterwards, the mice were randomly divided into a control group (Control, n=20), a model group (TAA, n=25), fed with conventional diet and conventional drinking water by using the digital table method. The TAA group was subcutaneously implanted with a pre-installed AngII micro slow-release pump (Alzet, 10370), and continuously released AngII 1000ng / (min Kg); the mice were dissected after the model was established, and the specimens were stored in liquid nitrogen and formaldehyde fixation, pathological sections and routine staining, the results showed that the elastic fibers of the aortic vessel wall were obviously destroyed and the lumen of the aortic vessel was obviously enlarged at the 4th week of embedding the pump, indicating that the modeling was succ...

Embodiment 3

[0062] Example 3: Correlation of TERT with VSMC phenotypes

[0063] VSMC were cultured in DMEM medium containing 10%, 5%, and 1% FBS for 48 hours, cell protein was extracted, and the expression of VSMC phenotypic markers and TERT were detected by Western blot. As the serum concentration decreased from 10% to 1%, the expression of VSMC synthetic phenotype marker OPN and PCNA representing cell proliferation ability was gradually down-regulated, and the expression of VSMC contractile phenotype marker SM22α was gradually up-regulated, accompanied by the gradual down-regulation of TERT expression. Add 1 μl of PDGF-BB at a concentration of 10 μg / ml to DMEM medium containing 5% FBS, culture VSMCs for 24 hours, 48 ​​hours, and 72 hours, extract cell proteins, and use Western blot to detect VSMC phenotypic markers and TERT expression ( image 3 A). B. With the increase of PDGF-BB stimulation time, the expression of OPN and PCNA is gradually up-regulated, and the expression of SM22α i...

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Abstract

The invention relates to the technical field of biology, in particular to application of a reagent for inhibiting expression of telomerase reverse transcriptase (TERT) in preparation of a medicine for preventing or treating thoracic aortic aneurysm. The invention reveals that the expression level of TERT in aorta media tissues is closely related to the pathogenesis process of thoracic aortic aneurysm for the first time, and verifies that inhibition of TERT can relieve the process of transformation of vascular smooth muscle cells (VSMCs) from a contraction phenotype to a synthetic phenotype, thereby providing a new target and medicine for prevention and treatment of thoracic aortic aneurysm.

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to the application of a reagent for inhibiting the expression of telomerase reverse transcriptase (TERT) in the preparation of medicaments for preventing or treating thoracic aortic aneurysm. Background technique [0002] Aortic aneurysm is a disease in which the structural changes of the aortic wall under the action of internal and external factors lead to progressive dilation of the aortic lumen, exceeding 50% of the normal diameter. Thoracic aortic aneurysm (TAA) is an aneurysm that occurs in the aortic sinus, ascending aorta, aortic arch, or descending aorta. Compared with other common cardiovascular diseases, although its incidence rate is low, due to its insidious onset, it is mostly asymptomatic in the early stage. As the disease progresses, thoracic aortic dissection or aneurysm rupture may occur and be life-threatening. At present, there are no early diagnosis methods and effe...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K31/713A61K31/7105A61P35/00A61P9/00
CPCA61K45/00A61K31/713A61K31/7105A61P35/00A61P9/00
Inventor 王国坤原野孙杨永阎岩韩林徐志云
Owner 中国人民解放军海军军医大学第一附属医院
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