在SARS-CoV-2中,S蛋白降低了细胞保护性防御,并促进了人类内皮细胞衰老
Alicia Villacampa1,2, Licia Shamoon1,2, Inés Valencia3
1Department of Pharmacology, School of Medicine, Universidad Autónoma de Madrid, Spain.
Aging and disease
|July 16, 2024
概括
SARS-CoV-2 S 蛋白质通过触发炎症和DNA损伤,直接导致血管过早衰老和内皮细胞衰老. 这一过程可以通过抑制NLRP3炎症酶或补充克洛托或血管素-1-7来预防.
科学领域:
- 心血管生物学 心血管生物学
- 传染性疾病 传染性疾病
- 细胞衰老 细胞衰老
背景情况:
- 血管过早衰老和内皮细胞衰老是心血管疾病和动脉血症并发症的关键风险因素,在急性和长期COVID-19中普遍存在.
- 对于病毒进入至关重要的SARS-CoV-2 S蛋白质已在感染后的几个月内被检测到在循环和组织中,这表明它在持续的血管问题中发挥了作用.
研究的目的:
- 为了调查SARS-CoV-2 S蛋白是否直接诱导内皮细胞衰老.
- 阐明S蛋白对血管衰老和功能障碍作出贡献的潜在机制.
主要方法:
- 人类静脉内皮细胞 (HUVEC) 的初级培养用SARS-CoV-2 S蛋白进行治疗.
- 评估了衰老标志物 (SA-β-gal,γH2AX),增长停止蛋白 (p53,p21,p16) 和细胞保护蛋白 (klotho,Nrf2,HO-1). 这些标志物包括:
- 在小鼠微血管中评估了依赖内皮细胞的血管松,并测试了MCC950,klotho和angiotensin-1-7等干预措施.
主要成果:
- 根据剂量,SARS-CoV-2 S蛋白增加了HUVEC中的衰老和DNA损伤标记物.
- S蛋白降低了保护性蛋白质 (klotho, Nrf2, HO-1) 的水平,以及血管功能受损.
- 抑制NLRP3炎症酶或用klotho/angiotensin-(1-7) 补充,可以逆转S蛋白的有害作用.
结论:
- SARS-CoV-2 S蛋白直接诱导内皮细胞衰老和血管功能障碍,导致COVID-19相关的血管并发症.
- 涉及的关键机制是NLRP3炎症酶,氧化应激和减少的细胞保护因子.
- 针对这些途径提供了潜在的治疗策略,以防止COVID-19的血管后续.
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