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Method for preventing and treating atherosclerosis through inhibition of micro-RNA155

A technology of micro-RNA155 and atherosclerosis, applied in the field of inhibiting micro-RNA155 for the prevention and treatment of atherosclerosis, can solve the problem of unclear role of microRNA

Inactive Publication Date: 2014-05-07
SHANGHAI INST OF BIOLOGICAL SCI CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] It is still unclear what role microRNA plays in atherosclerosis, so there is an urgent need to study the role and application of microRNA in the prevention and treatment of atherosclerosis

Method used

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  • Method for preventing and treating atherosclerosis through inhibition of micro-RNA155
  • Method for preventing and treating atherosclerosis through inhibition of micro-RNA155
  • Method for preventing and treating atherosclerosis through inhibition of micro-RNA155

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0137] In order to explore whether microRNAs are related to the pathology of atherosclerosis, the inventors first fed ApoE with high-fat diet - / - and wild-type mice, fed normal chow with ApoE - / - and wild-type mice for 10 weeks, the blood of the mice was obtained, and the supernatant was obtained by fractional centrifugation. The total RNA in the serum was further extracted with Trizol reagent, and fourteen microRNAs related to cardiovascular diseases were detected by real-time quantitative PCR.

[0138] The results showed that: ApoE fed a high-fat diet - / - The expression of miR-155 in the serum of mice was significantly higher than that of ApoE - / -mice, the expression of miR-146b-5p was next ( figure 1 A).

Embodiment 2

[0140] Existing technologies have proved that macrophages play an important role in the early stage of atherosclerosis by engulfing lipids to form foam cells. In order to explore whether miR-155 in blood is secreted from activated macrophages. Inventor, in the present embodiment, isolates the ApoE of high-fat feed feeding - / - ApoE in mice and normal chow fed - / - Macrophages of mice (n=6), and the expression level of miR-155 was detected.

[0141] The results showed that the expression of miR-155 was significantly higher in peritoneal macrophages of mice fed with high-fat diet than in those of mice fed with normal diet ( figure 1 B).

[0142] Macrophages were further isolated from the peritoneal cavity of wild-type mice, treated with oxLDL for 24 hours, and the total RNA in cells and cells secreted into the medium supernatant was extracted using TRIzol, and miR-155 was detected on cells and medium by real-time quantitative PCR expression levels in serum.

[0143] The result...

Embodiment 3

[0146] In order to further test how oxLDL induces the expression of miR-155 in macrophages, the inventors stimulated Raw264.7 cells by adding different doses of oxLDL at different time points.

[0147] The results showed that the expression of miR-155 in Raw264.7 cells increased significantly with time and dose ( figure 1 E. figure 1 F).

[0148] To further study the expression kinetics of miR-155 and its host gene BIC (pri-miR-155), Raw264.7 cells were stimulated with oxLDL at different time points within 16 h.

[0149] The results showed that: the expression of Pri-miR-155 increased rapidly at the beginning, reached the peak at two hours, and then decreased; on the contrary, the expression of miR-155 only increased 12 times at two hours, but it continued to increase within 16 hours, indicating that oxLDL regulates the expression of miR-155 at the transcriptional level ( figure 1 G).

[0150] Taken together, oxLDL induces the expression of miR-155 in macrophages and is as...

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Abstract

The invention relates to a method for preventing and treating atherosclerosis through inhibition of micro-RNA155. Specifically speaking, substantial rise of expression of miR-155 is positively correlated with severity of atherosclerosis; expression of miR-155 is greatly increased in peritoneal macrophages and serum of an atherosclerotic mouse (ApoE- / - / C57BL / 6J), and oxLDL can specifically induce expression and secretion of miR-155 by the peritoneal macrophages of the mouse. In oxLDL-induced macrophages, rise of the expression level of miR-155 promotes phagocytosis of lipids and generation of active oxygen; an miR-155 inhibitor can substantially inhibit plaque formation in aorta abdominalis of the mouse; miR-155 is an important target in treatment of atherosclerotic diseases, and the miR-155 inhibitor can be used for prevention and treatment of atherosclerosis.

Description

technical field [0001] The invention belongs to the field of biomedicine, in particular, the invention relates to a method for preventing and treating atherosclerosis by inhibiting micro-RNA155. Background technique [0002] Cardiovascular disease has gradually become the number one killer of human life, and the research on the mechanism of cardiovascular disease has always been a hot issue in life science research. Atherosclerosis (AS), a common disease of the cardiovascular and cerebrovascular systems, is a disease characterized by arterial damage caused by lipid deposition, smooth muscle cell proliferation, and calcification; it manifests as lipid and necrotic tissue Therefore, atherosclerosis is often considered to be a degenerative disease. It is now believed that atherosclerotic lesions are the result of the synergy of multiple factors. First, macrophages are recruited and attached to the inner wall of the aorta and transformed into foam cells; further, connective tis...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K39/395A61K38/00A61K48/00A61P9/10C12Q1/68
Inventor 荆清田福举李青王国坤邹俊
Owner SHANGHAI INST OF BIOLOGICAL SCI CHINESE ACAD OF SCI
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