单细胞和空间转录学 识别了脂肪酸结合蛋白,控制了肺高血压中的内皮糖解质和动脉编程
Bin Liu1,2,3,4, Dan Yi1,2,3, Shuai Li1,2,5
1Division of Pulmonary, Critical Care and Sleep, College of Medicine-Phoenix, University of Arizona, Phoenix. (B.L., D.Y., S.L., K.R., X.X., Y.C., H.Z., A.T., K.S.K., Z.D.).
Arteriosclerosis, thrombosis, and vascular biology
|May 22, 2025
概括
肺内皮细胞中的脂肪酸结合蛋白 (FABP4/5) 通过促进血管重塑来驱动肺动脉高血压 (PAH). 阻止FABP4/5可以缓解PAH症状,并预防右心力衰竭.
科学领域:
- 心血管研究研究心血管研究
- 肺高血压的发病因子 肺高血压的发病因子
- 内皮细胞生物学 内皮细胞生物学
背景情况:
- 肺动脉高血压 (PAH) 涉及血管重塑,导致右心力衰竭.
- 脂肪酸结合蛋白的内皮细胞表达 (FABP4/5) 被注意到,在PAH患者中FABP4升高.
- 目前尚不清楚内皮FABP4/5在PAH病原发生中的具体作用.
研究的目的:
- 调查内皮FABP4和FABP5在肺动脉高血压发展中的作用.
- 阐明FABP4/5介导的PAH病原性背后的细胞和分子机制.
主要方法:
- 从PAH患者和老鼠模型的肺动脉内皮细胞和肺组织中检查了FABP4/5表达.
- 分析了血蛋白质组,在小鼠模型 (CKO和TKO) 中进行了心声学,血液动力学,组织学和免疫染.
- 利用散装RNA测序,单细胞RNA测序和空间转录组学来理解分子机制.
主要成果:
- FABP4/5在PAH患者和模型的内皮细胞中受到高度诱导,与疾病严重程度相关.
- 在小鼠中FABP4/5的遗传删除减少了肺高血压,减弱了血管重塑,并预防了右心力衰竭.
- 删除FABP4/5使内皮细胞糖解和远端动脉编程正常化,减少氧化应激和HIF-2α,并抑制异常内皮细胞的增殖.
结论:
- 肺高血压诱导了FABP4/5在肺内皮细胞中的表达.
- 异常的FABP4/5表达促进内皮细胞糖解和远端动脉编程.
- 这有助于血管重塑,并加剧PAH的进展.
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