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Application of FABP3 to takayasu arteritis vascular fibrosis

A technology of FABP3 and Takayasu, which is applied in the field of biomedicine, can solve problems such as dyslipidemia and cardiovascular infection, and achieve the effects of reducing the incidence rate, taking it conveniently, and reducing cardiovascular adverse events

Pending Publication Date: 2021-08-13
ZHONGSHAN HOSPITAL FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] The technical problem to be solved by the present invention is: long-term use of large doses of glucocorticoids in the conventional treatment of Takayasu can lead to dyslipidemia, cause cardiovascular-related complications, and glucocorticoids combined with immunosuppressants can cause various infections and other problems.

Method used

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  • Application of FABP3 to takayasu arteritis vascular fibrosis
  • Application of FABP3 to takayasu arteritis vascular fibrosis
  • Application of FABP3 to takayasu arteritis vascular fibrosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0056] Curcuma granules (Guangdong Yifang Pharmaceutical Co., Ltd.) were used as adjuvant therapy for patients with Takayasu arteritis. After 6 months, the patient's imaging was stable and some of them improved:

[0057] 18 patients were enrolled in the group combined with adjuvant therapy with turmeric granules (average dose of glucocorticoid 10 mg / day + methotrexate 10-15 mg / week + turmeric granules 60 g / day). The baseline clinical characteristics are shown in Table 1. When compared with the baseline systemic vascular MRA images, 14 cases (78%) were found to be stable; 3 cases (17%) improved, and the baseline and 6-month systemic vascular MRA results of a 40-year-old male patient with Takayasu arteritis were as follows: figure 1 As shown, the stenosis of the right subclavian artery was significantly improved; only 1 case (6%) showed slight progress, indicating that the addition of curcuma granules had a good control effect on vascular disease and fibrosis in patients with Tak...

Embodiment 2

[0062] The differentially expressed gene FABP3 was verified by RNA-Seq screening:

[0063] In order to explore the potential molecular targets of curcumin in controlling vascular fibrosis in Takayasu arteritis, AAF was divided into three groups: ① NC control group ② HSP65 stimulation ③ HSP65 + curcumin three groups, and the total mRNA of each group was sequenced for transcriptome. ① ② Group comparison screened out 812 Differentially expressed genes, ②③ Comparison and screening of 3355 differentially expressed genes, and the intersection of the two parts of the differentially expressed genes, 215 differentially expressed genes were obtained, and the top 10 genes were verified by PCR. The results showed that FABP3 was most significantly up-regulated after HSP65 stimulation , and the down-regulation was most obvious after curcumin treatment, such as image 3 shown.

Embodiment 3

[0065] Adventitial FABP3 expression is closely related to vascular fibrosis in Takayasu arteritis:

[0066] By detecting the expression of FABP3 in the aortic specimens of 12 patients with Takayasu arteritis and 8 healthy controls, it was found that the expression of FABP3 in the affected arterial wall of patients with Takayasu arteritis was higher than that of healthy people, especially in the adventitia with severe fibrosis and thickening. ,Such as Figure 4 shown. In order to explore the relationship between FABP3 and vascular fibrosis, we detected the expression of arterial wall ECMs in patients with Takayasu arteritis and healthy people, and further selected three images randomly under high-power field of view for each patient's film, and calculated and analyzed the positive area with imageJ software (%), taking the average value, and carrying out correlation analysis, the results show that in Takayasu arteritis adventitia, the expression of FABP3 is positively correlate...

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Abstract

The invention discloses application of FABP3 to takayasu arteritis vascular fibrosis. According to the invention, by adding radix curcumae longae granules, the progress of the takayasu arteritis vascular fibrosis can be effectively controlled within 6 months, and the levels of pro-fibrotic factors FN1 and MMP9 in serum are reduced to a certain extent; and vascular adventitial fibroblasts (AAF) are transfected by using small interfering RNA and overexpression plasmids, down-regulation or overexpression of the AAF in FABP3 can respectively inhibit or promote expression and cell viability of a proliferation related gene Ki67 in cells, and meanwhile, can inhibit or promote synthesis of FN1, COL11A, COL1, MMP9 and MMP3 from the AAF. According to the invention, FABP3-OE-AAF is intervened in vitro by adopting curcumin, and the curcumin can inhibit the expression of FABP3 and meanwhile, can inhibit the synthesis of cell proliferation and vascular fibrosis related markers. The invention provides a new molecular target for clinical treatment of the takayasu arteritis vascular fibrosis.

Description

technical field [0001] The invention relates to the application of FABP3 in vascular fibrosis of Takayasu arteritis, and belongs to the technical field of biomedicine. Background technique [0002] Takayasu arteritis is a chronic non-specific, inflammatory disease of large vessels, mainly involving the aorta and its first-order branches, thoracic aorta, pulmonary artery and its branches, fundus arteries, and intracranial arteries can also be involved. Inflammation-driven vessel wall fibrosis is the main pathological feature of Takayasu arteritis, and fibrosis is the main cause of vital organ ischemia and organ failure. [0003] Clinically, 30-40 mg / day glucocorticoid plus immunosuppressants are used in the routine treatment of Takayasu arteritis, such as methotrexate 10-15 mg / week or leflunomide 20 mg / day or cyclophosphamide 600- 800mg / month, etc. These drugs suppress the immune system directly or indirectly, activate and inhibit inflammation, thereby effectively controllin...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K31/12A61K36/9066A61K31/7088A61P9/14A61K125/00
CPCA61K45/00A61K31/12A61K36/9066A61K31/7088A61P9/14A61K2300/00
Inventor 姜林娣吴思凡马莉莉陈慧勇
Owner ZHONGSHAN HOSPITAL FUDAN UNIV
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