消除衰老细胞可以促进肺高血压的发展和进展
Emmanuelle Born1, Larissa Lipskaia1, Marielle Breau1
1INSERM U955 and Département de Physiologie, Hôpital Henri Mondor, FHU SENEC, AP-HP, Créteil, France; Université Paris-Est Créteil (UPEC), France (E.B., L.L., M.B., A.H., D.P.B., E.M., G.D., S. Adnot, S. Abid).
Circulation
|December 14, 2022
概括
衰老细胞积聚在肺动脉高血压的肺部. 消除这些细胞使肺高血压恶化,这表明老化剂可能会损害肺血管.
科学领域:
- 心血管研究
- 细胞生物学
- 肺病学
背景情况:
- 衰老细胞 (SCs) 涉及到繁殖性疾病.
- 在肺高血压 (PH) 中SCs的具体作用尚不清楚.
研究的目的:
- 在肺高血压的人类和动物模型中调查SCs的存在和作用.
- 确定老化干预对已确定的肺高血压的影响.
主要方法:
- 在人类PH患者和小鼠模型中评估衰老和DNA损伤标志物 (p16,p21,γ-H2AX).
- 使用遗传和药理方法 (自杀基因,ABT263,FOXO4-DRI) 来消除小鼠和老鼠中的SC.
- 在小鼠中通过低氧,苏根或血清素载体过度表达引起的PH,在老鼠中通过单类药物.
主要成果:
- 人类PH肺部显示老化标志物和SCs增加,特别是在血管细胞中.
- 在小鼠中,低氧和PH诱导增加了SC标志物和肺内皮细胞 (P- EC) 衰老.
- 排泄SC导致右心室压力和缩,增加了血管重塑,并减少了P-EC.
- 在多种动物模型中,老化治疗加剧了PH严重性和P- EC损失.
结论:
- 通过老化干预消除衰老的P-EC可以加剧肺高血压.
- 针对细胞衰老的策略需要仔细考虑它们对肺血管健康的影响.
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