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高密度脂蛋白通过通过miRNA-181a-5p影响自性来调节血管生成
Bi-Ang Kang1,2,3,4, Hua-Ming Li1,2,3,4, Ya-Ting Chen1,2,3,4
1Division of Cardiac Surgery, Cardiovascular Diseases Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
Science China. Life sciences
|October 28, 2023
概括
正常的高密度脂蛋白 (nHDL) 通过抑制miR-181a-5p刺激血管生成,促进自和eNOS表达. 功能障碍的高密度胆固醇 (dHDL) 通过增加miR-181a-5p,抑制自和eNOS,从而损害血管生成.
科学领域:
- 心血管生物学 心血管生物学
- 细胞和分子医学是细胞和分子医学.
- 生物化学 生物化学
背景情况:
- 高密度脂蛋白 (HDL) 在血管生成中起着双重作用,正常的HDL (nHDL) 促进它,冠状动脉疾病患者的HDL (dHDL) 损害它.
- 自对于血管生成至关重要,而HDL对自的调节是研究的一个关键领域.
- 通过nHDL和dHDL影响自并随后影响血管生成的具体机制尚不清楚.
研究的目的:
- 研究nHDL和dHDL是否通过调节自来调节血管生成.
- 阐明微RNA (miRNA) 和自相关蛋白5 (ATG5) 在高密度脂介导的内皮细胞功能调节中的作用.
- 探索针对血管新生功能障碍的HDL介导自的治疗潜力.
主要方法:
- 用nHDL和dHDL对待内皮细胞 (ECs),有或没有自抑制剂,以评估自,eNOS表达,miRNA配置文件,氧化 (NO) 生产,超氧化 (O2•−) 生产和细胞迁移/管形成.
- 使用分子生物学技术研究了miR-181a-5p和ATG5之间的直接向关系.
- 利用高胆固醇低密度脂蛋白受体零 (LDLr-/-) 小鼠和C57BL/6小鼠在体内评估ATG5表达和血管生成.
主要成果:
- nHDL抑制了miR-181a-5p,增强了自,eNOS表达,NO生产和EC迁移/管形成,同时减少了O2•−生成.
- dHDL表现出相反的效果,增加miR-181a-5p,抑制自和eNOS,减少NO产量,并损害EC迁移/管形成.
- ATG5被确定为miR-181a-5p的直接标;它的调制模仿或逆转nHDL和dHDL对血管生成和自的影响.
结论:
- nHDL通过抑制miR-181a-5p促进血管生成,从而刺激自和eNOS表达,从而导致NO的产生增加.
- dHDL通过增加miR-181a-5p来抑制血管生成,这抑制了自和eNOS,减少了NO并增加了氧化应激.
- 这些发现揭示了HDL介导血管生成通过自调节的新机制,并确定ATG5和miR-181a-5p作为潜在的治疗点.
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