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在肺高血压中,内皮细胞转化为介质细胞

Benoît Ranchoux¹, Fabrice Antigny¹, Catherine Rucker-Martin¹

¹From Univ. Paris-Sud, Faculté de médecine, Kremlin-Bicêtre, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); AP-HP, DHU TORINO, Centre de Référence de l'Hypertension Pulmonaire Sévère, Service de Pneumologie et Réanimation Respiratoire, Hôpital Bicêtre, Le Kremlin-Bicêtre, France (B.R., F.A., C.R.-.M., A.H., P.D., F.L., G.S., M.H., S.C.-K., F.P.); INSERM UMR-S 999, Labex LERMIT, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (B.R., F.A., C.R.-M., A.H., P.D., F.L., E.F., G.S., M.H., S.C.-K., F.P.); INRA U1196, Génomique et Physiologie de la Lactation - Plateau de Microscopie Electronique à Transmission, Jouy-en-Josas, France (C.P., S.C.); Service de Chirurgie Thoracique, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France (E.F.); Service d'Anatomie Pathologique, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France (P.D., S.P.); Department of Pulmonary Medicine, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands (H.J.B.); INSERM UMR 1064-Center for Research in Transplantation and Immunology-ITUN et Transgenic Rats and Immunophenomic Platform, Nantes, France (S.R., I.A.); and INSERM U955, Département de Physiologie and Service de Cardiologie, Hôpital Henri Mondor, AP-HP, Université Paris-Est Créteil (UPEC), Créteil, France (A.H., S.A.).

|January 17, 2015

概括

内皮转介质转换 (EndoMT) 通过改变BMPR2信号传递,有助于肺动脉高血压 (PAH) 血管重塑. 这个过程是可用药的,为PAH提供了潜在的新疗法.

科学领域:

心血管生物学心血管生物学
细胞生物学细胞生物学
分子医学是分子医学.

背景情况:

肺动脉高血压 (PAH) 的特点是血管重塑和α-平滑肌肉表达actin的细胞的积累.
内皮转介质转换 (EndoMT) 是PAH中这些细胞的潜在来源.

研究的目的:

调查EndoMT在人类PAH血管改造中的作用.
阐明将EndoMT与PAH联系起来的分子机制,特别是关于BMPR2信号传递.
探索针对PAH中的EndoMT的治疗策略.

主要方法:

对焦显微镜,传输电子显微镜和相关光和电子显微镜用于in situ分析.
在体外研究中使用人类肺动脉内皮细胞和动物模型 (单克罗他林,SuHx).
定量实时PCR,西斑,以及一种新的BMPR2突变大鼠模型 (BMPR2(Δ140Ex1/+)).

主要成果:

人类PAH中EndoMT的in situ和in vitro证据,在动物模型中得到证实.
恩多MT与BMPR2信号改变有关,扭曲过度表达和维丁酸化被确定为关键分子参与者.
拉巴胺部分逆转了EndoMT标记物,改善了实验PAH,并减少了内皮细胞迁移.

结论:

内皮细胞到介质细胞的过渡与PAH的封闭性血管重塑有关.
BMPR2信号的改变与PAH中的EndoMT有关.
向EndoMT为PAH提供了一个潜在的治疗途径.

关键词:

人类TWIST1蛋白质,人类骨形态遗传蛋白质受体,II型的受体.心血管疾病心血管疾病表皮细胞-介质细胞过渡.高血压,肺部高血压,肺部高血压.模型,动物模型,动物模型.新的亲密关系这是西洛利斯 (sirolimus).血管改造血管改造血管改造在这里,你会发现Vimentin.

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