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Medicinal uses of plastin t

A drug, the technology of PLS3-C566A, is used in the prevention and treatment of aortic dissection to achieve the effect of improving vascular endothelial dysfunction

Active Publication Date: 2022-03-08
NANJING MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, whether plastin3 and the thiol-nitrosylation modification of plastin3 play a regulatory role in aortic dissection and its specific mechanism have not been reported yet.

Method used

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  • Medicinal uses of plastin t
  • Medicinal uses of plastin t
  • Medicinal uses of plastin t

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Example 1 Correlation detection between aortic dissection and plastin3 in endothelial cells

[0026] In order to investigate whether aortic dissection affects the modification level of plastin3 in endothelial cells, the level of thiol-nitrosylation modification of aortic plastin3 in patients with clinical aortic dissection and cadaveric donors without cardiovascular disease was detected by biotin conversion method (biotin-switch) joint Western blot detection results are as follows figure 1 as shown, figure 1 Among them, PLS3 represents the content of plastin T (plastin3), and SNO-PLS3 represents the content of plastin T modified by thiol nitrosylation; figure 1 It can be seen that the level of thiol nitrosylation modification of plastin3 was significantly increased in patients with aortic dissection.

[0027] The Western blot detection method is a conventional technique in the art, for details, please refer to the literature: "BurnetteWN. Western blotting: electrophor...

Embodiment 2

[0031] Example 2 Inhibition of thiol-nitrosylation modification of plastin3 to improve endothelial dysfunction in aortic dissection

[0032] In order to further study whether the sulfhydryl nitrosylation modification of plastin3 is involved in the occurrence of endothelial dysfunction in aortic dissection at the cellular level, this example uses Lipofectamine 3000 (Invitrogen) in HUVEC cells and transfected PLS3-WT according to the instructions and PLS3-C566A plasmid for 24 h, and then treated with Ang II (100 nM) for 24 h to detect the change of endothelial cell function, the results are shown in the attached Figure 4-7 Shown:

[0033] in, Figure 4 Schematic diagram of overexpression of PLS3-WT and PLS3-C566A plasmids in HUVEC cells for 24 hours, and then treated with Ang II (100 nM) for 24 hours, Figure 4 It was found that overexpression of PLS3-C566A could significantly attenuate Ang II-induced lamellipodia formation in endothelial cells.

[0034] Figure 5 Schematic...

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Abstract

The invention provides a medical application of thiol nitrosylation modification of filament protein T (Plastin3, PLS3), which relates to the cardiovascular field; the level of Plastin3 thiol nitrosylation modification in the vascular tissue of human aortic dissection increases, and the thiol nitrosylation modification level in cells Ang II induces the modification of PLS3 in endothelial cells, and its modification site is at cysteine ​​566. At the animal level, BAPN was used to create aortic dissection model, and endothelial cell-specific overexpression of PLS3‑C566A improved the main function of modeled mice. Formation of arterial dissection and aortic relaxation function; the present invention provides the application of plastin T in the preparation of drugs for the treatment of endothelial dysfunction in aortic dissection, especially the inhibition of the thiol nitroso group of cysteine ​​566 of plastin T The application of biocarriers with modified levels in the preparation of drugs for the treatment of aortic dissection vascular endothelial dysfunction, the present invention has opened up new drug applications for aortic dissection vascular dysfunction, and provides useful research and development for the prevention and treatment of aortic dissection vascular dysfunction meaningful reference.

Description

technical field [0001] The invention belongs to the technical field of prevention and treatment of aortic dissection, and specifically relates to the application of regulating the sulfhydryl nitrosylation modification of plastin3 in the prevention and treatment of aortic dissection vascular endothelial dysfunction. Background technique [0002] Aortic dissection is a fatal disease in which rupture of the aorta can lead to sudden death. Aortic dissection arises from a tear in the intima of the aorta, exposing the media to the blood flow. Hypertension is the main risk factor for aortic dissection, and about 80% of patients with aortic dissection are accompanied by hypertension. In patients with aortic dissection, the level of Ang II in the body is significantly increased. Ang II can cause contraction of vascular smooth muscle cells and endothelial cell dysfunction, increase blood pressure, and promote vascular remodeling, thereby leading to vascular diseases. Surgical repai...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K38/17A61P9/14
CPCA61K38/17A61P9/14
Inventor 季勇陈钰榕张佳苗子安潘丽虹林喆谢利平
Owner NANJING MEDICAL UNIV