PEAR1受体在血管内皮损伤修复和血管新生中的作用机制及潜在药物新靶点的研究
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中文摘要
申请人对血小板受体PEAR1进行了长期深入的研究,前期发现PEAR1在血小板黏附活化中发挥了重要的作用,影响血小板聚集和抗血小板药物的药效。近年有报道PEAR1在血管内皮高表达,调控血管内皮细胞损伤修复和血管新生,但PEAR1该能力在各种生理病理状态下如何体现、是否有组织特异性、作用机制尚缺乏研究。本课题首先利用pear1基因敲除小鼠通过后肢缺血、皮肤伤口愈合、口腔溃疡愈合、动脉粥样硬化斑块/心脏新生血管、肝脏原位移植瘤模型实验,明确在不同组织、病理状态下PEAR1调控内皮损伤修复和血管新生的能力差异并进行机理研究;在人体水平,采集下肢动脉闭塞患者病变和正常血管组织、肝细胞癌患者肝癌细胞组织,分析PEAR1及相关基因蛋白表达、mRNA水平、甲基化、PEAR1rs12041331基因型与病变或癌细胞能力的相关性,从动物和人体水平评估PEAR1作为药物新靶点的潜力。
英文摘要
Our previous studies found that PEAR1 plays an important role in platelet adhesion activation, which affects platelet aggregation and antiplatelet drug’s efficacy. Recent years, it has been reported that PEAR1 is highly expressed in vascular endothelium, which can regulate the injury impairing of vascular endothelial cell and angiogenesis. However, how PEAR1 is manifested in various physiological and pathological conditions, whether it is tissue-specific, and the mechanism of its action is still not clear. To identify the ability of PEAR1 in different tissues and pathological conditions and to clarify the mechanism, this study uses Pear1-knockout mice to build hind limb ischemia, skin wound healing, oral ulcer healing, atherosclerotic plaque, cardiac neovascularization, and liver orthotropic transplantation models firstly. Then, we collect the lesions of the lower extremity arterial occlusion, the vascular tissue of the adjacent segment, and the liver cancer cell tissue of the primary liver cancer patient at the human body level. Finally, we detect the patient genome, PEAR1 rs1201331 gene of different tissue cells, compare PEAR1 expression levels between tissue and platelet-rich plasma, and evaluate the potential and application of PEAR1 as a novel drug target from both animal and human levels.
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DOI:10.1002/ctm2.1263
发表时间:2023-05
期刊:Clinical and translational medicine
影响因子:10.6
作者:
通讯作者:
DOI:10.1002/phar.2736
发表时间:2022-10
期刊:Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy
影响因子:--
作者:Q. Xiang;Zhe Wang;Guangyan Mu;Qiu-fen Xie;Zhiyan Liu;Shuang Zhou;Hanxu Zhang;Zi-ning Wang;Kun Hu;Hongtao Song;Dongdong Yuan;Q. Xia;Yan Huang;Yi-min Cui
通讯作者:Q. Xiang;Zhe Wang;Guangyan Mu;Qiu-fen Xie;Zhiyan Liu;Shuang Zhou;Hanxu Zhang;Zi-ning Wang;Kun Hu;Hongtao Song;Dongdong Yuan;Q. Xia;Yan Huang;Yi-min Cui
Genetic variations in relation to bleeding and pharmacodynamics of dabigatran in Chinese patients with nonvalvular atrial fibrillation: A nationwide multicentre prospective cohort study.
中国非瓣膜性心房颤动患者与出血和达比加群药效学相关的遗传变异:一项全国性多中心前瞻性队列研究
DOI:10.1002/ctm2.1104
发表时间:2022-12
期刊:Clinical and translational medicine
影响因子:10.6
作者:
通讯作者:
Effect of Genetic Polymorphism Including NUP153 and SVEP1 on the Pharmacokinetics and Pharmacodynamics of Ticagrelor in Healthy Chinese Subjects
NUP153和SVEP1基因多态性对中国健康受试者替格瑞洛药动学和药效学的影响
DOI:10.1007/s40261-022-01154-6
发表时间:2022-04
期刊:Springer Nature
影响因子:--
作者:Qian Xiang;Zhiyan Liu;Guangyan Mu;Qiufen Xie;Hanxu Zhang;Shuang Zhou;Zining Wang;Ninghong Guo;Jie Huang;Jie Jiang;Jian Li;Guoping Yang;Yimin Cui
通讯作者:Yimin Cui
DOI:10.3390/genes13101867
发表时间:2022-10-15
期刊:Genes
影响因子:3.5
作者:
通讯作者:
PEAR1受体对血小板和血管内皮细胞双重调控作用机制研究及配体发现
- 批准号:--
- 项目类别:面上项目
- 资助金额:52万元
- 批准年份:2022
- 负责人:向倩
- 依托单位:
基于PEAR1受体功能和基因的抗血栓药理新靶点研究
- 批准号:81673509
- 项目类别:面上项目
- 资助金额:25.0万元
- 批准年份:2016
- 负责人:向倩
- 依托单位:
基于GPIIb/IIIa遗传多态性的抗血栓药物个体化治疗研究
- 批准号:81202592
- 项目类别:青年科学基金项目
- 资助金额:24.0万元
- 批准年份:2012
- 负责人:向倩
- 依托单位:
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