李纪君,谭延振,杨红燕,周嘉恒,丁 昕,李宸涵,张鹏飞,吴方琴,高 峰,李 敏,张 星.内皮特异性miR-342-5p敲除致小鼠内皮损伤和心血管功能紊乱[J].,2022,(8):1408-1412 |
内皮特异性miR-342-5p敲除致小鼠内皮损伤和心血管功能紊乱 |
Endothelium-specific miR-342-5p Knockout Induces Vascular Endothelial Dysfunction and Cardiovascular Dysfunction in Mice |
投稿时间:2021-11-10 修订日期:2021-11-30 |
DOI:10.13241/j.cnki.pmb.2022.08.002 |
中文关键词: miR-342-5p 内皮细胞 心血管功能 凋亡 |
英文关键词: MiR-342-5p Endothelial cells Cardiovascular function Apoptosis |
基金项目:国家自然科学基金项目(31871146;32071169);陕西省自然科学基金项目(2020JQ-442) |
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中文摘要: |
摘要 目的:我们前期研究发现有氧运动促进内皮细胞等分泌miR-342-5p,miR-342-5p通过外泌体富集至心肌细胞后发挥心脏保护作用。本研究的主要目的是明确内皮来源的miR-342-5p在心血管功能调控中的作用。方法:我们构建了内皮特异性miR-342-5p敲除小鼠,通过心脏超声检测和血管收缩舒张功能检测观察了该小鼠心血管功能的变化;培养血管内皮细胞,通过对细胞存活率检测、相关蛋白的表达检测等方法对miR-342-5p发挥心血管保护作用的机制进行探究。结果:内皮miR-342-5p敲除致小鼠运动能力降低、心脏收缩功能不变,但舒张功能紊乱。且内皮miR-342-5p敲除致小鼠血管口径变小、微血管密度降低和血管内皮功能紊乱。内皮miR-342-5p敲除致小鼠心血管功能紊乱的机制与其引起的内皮细胞损伤有关。敲低miR-342-5p致内皮细胞中caspase 9水平增加,引起内皮细胞活性降低和凋亡增加。结论:这些结果进一步证实了内皮细胞来源的miR-342-5p在心血管功能中的重要作用,提示miR-342-5p在防治心血管疾病中的潜在应用。 |
英文摘要: |
ABSTRACT Objective: We previously found that aerobic exercise protects the heart through secreting miR-342-5p from endothelial cells and others. The aim of the study is to test the role of miR-342-5p in cardiovascular function and its underlying mechanism. Methods: An endothelium-specific miR-342-5p knockout mice model was established. The echocardiography and vasodilation in isolated aortas were detected. Cell viability and apoptosis-related protein contents in endothelial cells were tested to explore the underlying mechanism. Results: Endothelium-specific miR-342-5p knockout decreased the exercise capacity, and cardiac diastolic function, although the cardiac systolic function was unchanged. In addition, it decreased the capillary density in the heart and induced endothelial dysfunction. The cardiovascular dysfunction induced by miR-342-5p knockout may attribute to the endothelial injury induced by miR-342-5p deficiency in endothelial cells. Knockdown of miR-342-5p increased the content of caspase 9, decreased the cell viability and promoted apoptosis in cultured endothelial cells. Conclusion: These results suggested that endothelium-derived miR-342-5p plays an important role in cardiovascular function, and highlights the potential of miR-342-5p in treatment of cardiovascular disease. |
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