Application of recombinant P-selectin glycoprotein ligand 1 as a target in preparation of drugs for preventing and/or treating aneurysms

Abstract

The invention relates to the field of biomedicine, in particular to the application of recombinant P-selectin glycoprotein ligand 1 as a target in preparation of drugs for preventing and / or treating aneurysms. PSGL-1 gene knockout mice are taken as a research object. Compared with wild-type mice, the PSGL-1 gene knockout mice has the characteristics that the incidence of thoracic aortic aneurysm and abdominal aortic aneurysm is significantly reduced, collagen deposition is reduced, elastic fiber breakage and smooth muscle cell degradation are significantly inhibited, infiltration of inflammatory cells is significantly reduced, and expression of inflammatory factors, fibrotic factors and adhesion molecules is significantly inhibited. In addition, the adhesion of peripheral blood mononuclearcells to endothelial cells in the absence of PSGL-1 is also significantly reduced. The invention reveals that the loss of PSGL-1 has the effect of inhibiting aneurysms, and a theoretical basis and clinical basis are provided for the role of PSGL-1 in studying new targets and new strategies for preventing and treating aneurysms.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to the application of P-selectin glycoprotein ligand-1 as a target in the preparation of drugs for preventing and / or treating aneurysms. Background technique [0002] Aortic aneurysms can be divided into thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA) according to the location of the disease. TAA occurs in people of all ages, with similar incidence in men and women, and is highly related to genetic factors. In contrast, the usual occurrence of AAA was associated with aging, male sex, atherosclerosis and smoking, but with weaker genetic associations. AAA, the most common form of aortic aneurysm, occurs in adults over the age of 50 and occurs more frequently in men than in women. Aneurysm rupture is the most dangerous complication of abdominal aortic aneurysm and the leading cause of death in patients. Currently, open surgical repair and endovascular repair are the onl...

AI Technical Summary

Problems solved by technology

[0007] Disadvantages of open surgical repair and endovascular repair for aneurysm: Surgical treatment has indications, not all patients are suitable for open surgery or endovascular repair; surgical treatment is risky, and aneurysm itself is a high-risk disease. The risk is sometimes even higher than the risk caused by aneurysm complications

[0020] Existing drugs are currently concentrated in the animal test or clinical trial stage, and some drugs have produced controversial results in the clinical trial stage. By targeting inflammatory cells and inflammatory cytokines, the therapy is aimed at the terminal stage of the inflammatory response. Inflammation is not controlled from the initial stage of the inflammatory response, only to delay the weakening effect, and cannot fundamentally inhibit the occurrence of aneurysms

Protease inhibitor drugs also act on the formed protease, and cannot inhibit the initial steps of aneurysm formation, while antithrombotic drugs only inhibit aneurysms containing thrombus, and antithrombotic therapy Therapeutic effect needs to be determined by the advancement of clinical trials

Although renin-angiotensin system inhibitory drugs have been undergoing clinical trials, the results of clinical trials are not completely consistent, and their therapeutic effects on aneurysms are controversial

[0021] In summary, despite decades of research on AAA, there is a lack of understanding of the pathogenesis and factors of AAA. Therefore, it is important to elucidate the molecular basis of this disease, find new therapeutic targets, and develop drugs that effectively inhibit the development of aneurysms. Effective drugs have important practical significance for aneurysm research

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