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Medicinal uses of choline transporter 2

A technology for transporter and choline, which is applied in the application field of regulating choline transporter 2 in the prevention and treatment of aortic dissection, can solve the problems of choline transporter 2 regulation and unclear specific mechanism of action, and achieves inhibition of dedifferentiation. , restore physiological function, inhibit the effect of increased activity

Active Publication Date: 2020-12-08
NANJING MEDICAL UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Our mass spectrometry results found that the protein level of choline transporter 2 in the vascular tissues of patients with aortic dissection was significantly increased, but whether choline transporter 2 regulates the vascular lesions of aortic dissection and the specific mechanism is still unknown. It is clear, meanwhile, whether gene therapy using overexpressed choline transporter 2 plays a therapeutic role in aortic dissection has not yet been reported

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  • Medicinal uses of choline transporter 2
  • Medicinal uses of choline transporter 2
  • Medicinal uses of choline transporter 2

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0017] Under the pathological conditions of aortic dissection, the expression of CTL2 was significantly increased.

[0018] First, we used Western Blot to detect that compared with the control group, the expression of smooth muscle contractile markers α-smooth muscle actin and calmodulin-1 decreased significantly in the vascular tissues of patients with aortic dissection. At the same time, choline The expression of transporter 2 (gene sequence number: 57153, link: https: / / www.ncbi.nlm.nih.gov / gene / ?term=57153) was significantly increased in the vascular tissues of patients with aortic dissection ( figure 1 : A), further immunofluorescence experiments found that the expression of choline transporter 2 was significantly increased mainly in the smooth muscle cells of patient tissues ( figure 1 : B). We are in ApoE - / - Angiotensin II microosmotic pump was administered to mice to induce aortic dissection model, aortic vascular tissue was taken, and immunofluorescence also found t...

Embodiment 2

[0020] Knockdown of cholinergic transporter 2 at the cellular level leads to aortic dissection, and overexpression of cholinergic transporter 2 delays the progression of aortic dissection.

[0021] We further used siRNA to knock down choline transporter 2 in human aortic smooth muscle cells. RT-PCR detection found that the expression of smooth muscle cell contractility markers Fbn1, Cnn1, Smth, Tagln, and Acta2 decreased significantly, and synthetic markers The expressions of Opn and Klf4 were significantly increased, and the expressions of matrix metalloproteinases MMP2 and MMP9 were significantly increased ( Figure 4 ). In situ zymography experiments found that after angiotensin II treatment in human aortic smooth muscle cells, the activity of matrix metalloproteinase 2 / 9 was significantly increased; on this basis, after knocking down choline transporter 2, matrix metalloproteinase The activity was further increased, and the matrix metalloproteinase activity was inhibited ...

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Abstract

The invention discloses medical application of choline transport protein 2, and relates to the cardiovascular field. The aortic choline transport protein 2 expression of aortic dissection patients issignificantly up-regulated. An aortic dissection model is constructed at the cell and animal level, and increase expression of smooth muscle choline transport protein 2 is found. The choline transportprotein 2 is knocked down in human aortic smooth muscle, the level of a smooth muscle contractile marker is reduced, a synthetic marker and matrix metalloproteinase are increased, and obvious dedifferentiation occurs. Overexpression of choline transport protein 2 can reduce the activity of matrix metalloproteinase and delay the process of aortic dissection, prompts that the choline transport protein 2 plays a protective role in aortic dissection, and is beneficial to discovery of a new marker of aortic dissection. According to the invention, a new prevention and treatment method for aortic dissection is developed, and a significant reference is provided for development of a novel medicine for aortic dissection.

Description

technical field [0001] The invention belongs to the technical field of prevention and treatment of aortic dissection, and in particular relates to the application of regulating choline transporter 2 in the prevention and treatment of aortic dissection. Background technique [0002] Aortic dissection refers to the tearing of the aortic intima, blood flows into the aortic wall through the tear, and the media is peeled off from the adventitia, thereby forming a false lumen attached to the vessel wall. The main pathological features of aortic dissection are degradation of vascular matrix and rupture of elastic fiber layer. The etiology can be divided into genetic factors such as matrix metalloproteinase Fibrillin 1, smooth muscle actin MYH11, TGF signal TGFβR1 / 2 gene mutation, etc., and environmental factors such as arterial Atherosclerosis, hypertension, smoking and metabolism, etc. A variety of pathogenic factors such as increased matrix degradation, especially the up-regulat...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): G01N33/68A61K38/17A61P9/00
CPCA61K38/17A61P9/00G01N33/6893G01N2333/705G01N2800/329
Inventor 季勇谢利平宋天宇赵爽
Owner NANJING MEDICAL UNIV