以TRIM25为媒介的XRCC1无处不在加速动脉样硬化,通过诱导巨细胞M1极化和编程死亡来加速动脉样硬化
Hongxian Wu1, Wei Gao1, Yuanji Ma1
1Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Fudan University, Shanghai, China.
概括
该研究显示,TRIM25调节巨细胞死亡途径,特别是热和死,影响动脉样硬化进展. 针对TRIM25-XRCC1-PARP1轴为心血管疾病提供了潜在的治疗策略.
科学领域:
- 心血管生物学 心血管生物学
- 免疫学 免疫学 免疫学
- 分子医学是分子医学.
背景情况:
- 巨细胞增生对于血管稳定至关重要,但可以触发巨细胞死亡,这一过程对动脉样硬化有不清楚的影响.
- 在调节巨细胞命运和其与动脉样硬化进展的联系中,TRIM25 (E3泛素酶) 的作用在很大程度上仍未被阐明.
研究的目的:
- 研究TRIM25在动脉样硬化期间巨细胞死亡中的作用.
- 阐明将TRIM25与巨细胞重编程和血管炎症联系起来的分子机制.
主要方法:
- 在患有冠状动脉疾病的患者中测量了血清TRIM25水平.
- 具有和没有TRIM25删除的Apoe-/-小鼠被食高脂肪饮食以评估动脉样硬化发展.
- 使用RNA-seq,PCR,西部斑点和FACS分析了巨细胞死亡途径 (热,死) 和信号传递.
主要成果:
- 在患有慢性全闭性病变的患者和高脂肪饮食诱导的小鼠大动脉中,TRIM25的下调.
- 在小鼠中,TRIM25缺乏减少了动脉样硬化斑块大小,炎症和纤维化.
- 在巨细胞中,TRIM25删除调节了灭和灭的途径,降低了PARP1和RIPK3的表达;XRCC1上调抑制了PARP1的活性.
结论:
- TRIM25-XRCC1-PARP1-RIPK3轴对于调节巨细胞死亡和动脉样硬化的进展至关重要.
- 通过这一轴准巨细胞重编程具有预防动脉样硬化发展的治疗潜力.
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