高密度脂蛋白通过长非编码RNA HDRACA 调节血管生成
Zhi-Wei Mo1,2,3, Yue-Ming Peng1,2, Yi-Xin Zhang2,4
1Division of Cardiac Surgery, Cardiovascular Diseases Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Signal transduction and targeted therapy
|August 13, 2023
概括
正常的高密度脂蛋白 (HDL) 通过降低HDRACA的调节来促进血管形成. 功能障碍的HDL无法抑制HDRACA,这解释了其诱导血管生成的能力降低.
科学领域:
- 分子生物学分子生物学
- 心血管研究研究心血管研究
- 在RNA生物学,RNA生物学.
背景情况:
- 正常的高密度脂蛋白 (nHDL) 促进血管生成,但冠状动脉疾病患者的功能障碍的HDL (dHDL) 失去了这种能力.
- 在HDL调节血管生成的基础机制和功能障碍的HDL的作用仍然不完全理解.
研究的目的:
- 为了识别参与高脂介导血管生成的新型分子调节剂.
- 阐明长非编码RNA,HDRACA在nHDL和dHDL对血管生成的差异性影响中的作用.
主要方法:
- 研究了HDL,内皮细胞和HDRACA表达之间的相互作用.
- 利用了分子生物学技术,包括RNA测序,蛋白质无化试验和mRNA-蛋白质结合分析.
- 采用后肢缺血小鼠模型来评估HDRACA在血管生成中的体内功能.
主要成果:
- 在内皮细胞中,nHDL通过S1P受体1和WW域含有E3无素蛋白联酶2降低HDRACA的表达,以克鲁佩尔样因子5为目标.
- dHDL,具有较低的sphingosine 1-phosphate (S1P) 水平,在降低HDRACA的调节方面效果较差.
- HDRACA通过与Ras相互作用蛋白1 (RAIN) 相互作用来抑制血管生成,破坏RAIN-维吉林相互作用,并因此减少与维吉林结合的增殖细胞核抗原 (PCNA) mRNA.
- 在小鼠模型中,HDRACA的过度表达导致血管新生恢复受损.
结论:
- 在HDL的血管生成调节中,HDRACA是关键的调解者.
- 通过抑制HDRACA表达,nHDL诱导血管生成,而dHDL减少的能力解释了其血管功能障碍.
- HDRACA代表了心血管疾病的潜在治疗点,其特点是血管生成受损.
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