急性损伤破坏了通过SerpinA3N的心脏重塑
Gowda S Pramod1, Stanely Qu1, Runze Ni1
1Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida (USF), Tampa, Florida, USA.
bioRxiv : the preprint server for biology
|September 26, 2025
概括
急性损伤 (AKI) 可以损害心脏. 这项研究揭示了AKI上调SerpinA3N,抑制Granzyme B,这促进了心脏纤维化和重塑.
科学领域:
- 心脏病学 心脏病学
- 腎臟病學 (nephrology) 是一種醫學專業.
- 分子生物学分子生物学
背景情况:
- 3型心脏病综合征 (CRS-3) 或急性心综合征,将急性损伤 (AKI) 与心脏功能障碍联系起来.
- 导致AKI引起的心脏损伤的确切机制尚不清楚.
研究的目的:
- 调查心肌前纤维化因子发展和AKI后心脏重塑背后的分子机制.
- 探索SerpinA3N和Granzyme B在AKI相关心脏变化的作用.
主要方法:
- 使用小鼠模型的AKI诱导双边脚紧和再注射.
- 在心脏组织上进行蛋白质组分析 (LC-MS) 和RNA测序 (RNA-seq).
- 在心脏组织和H9C2细胞中评估了血清蛋白酶活性,基因表达,蛋白质水平和细胞因子表达.
主要成果:
- AKI显著提高了心脏SerpinA3N表达的调节,与血清蛋白酶 (Granzyme B) 活性相反相关.
- AKI诱导了亲纤维化因素,线粒体功能障碍和心脏炎症.
- 在H9C2细胞中使用XAV939抑制SerpinA3N增强了Granzyme B活性.
结论:
- AKI通过SerpinA3N介导的抑制Granzyme B活性促进心脏纤维化和不良重塑.
- 调节SerpinA3N水平可能提供一种治疗策略,以减轻AKI诱导的心脏纤维化和改善细胞外基因组合.
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