Choquet Caroline, Kelly Robert G, Miquerol Lucile
Aix-Marseille Université, CNRS UMR 7288, IBDM, Marseille, France.
Pediatr Cardiol. 2019 Oct;40(7):1331-1338. doi: 10.1007/s00246-019-02161-9. Epub 2019 Jul 24.
Left ventricular noncompaction (LVNC) is a genetically heterogeneous disorder the etiology of which is still debated. During fetal development, trabecular cardiomyocytes contribute extensively to the working myocardium and the ventricular conduction system. The impact of developmental defects in trabecular myocardium in the etiology of LVNC has been debated. Recently we generated new mouse models of LVNC by the conditional deletion of the key cardiac transcription factor encoding gene Nkx2-5 in trabecular myocardium at critical steps of trabecular development. These conditional mutant mice recapitulate pathological features similar to those observed in LVNC patients, including a hypertrabeculated left ventricle with deep endocardial recesses, subendocardial fibrosis, conduction defects, strain defects, and progressive heart failure. After discussing recent findings describing the respective contribution of trabecular and compact myocardium during ventricular morphogenesis, this review will focus on new data reflecting the link between trabecular development and LVNC.
左心室心肌致密化不全（LVNC）是一种遗传异质性疾病，其病因仍存在争议。在胎儿发育过程中，小梁心肌细胞对工作心肌和心室传导系统有广泛贡献。小梁心肌发育缺陷在LVNC病因中的影响一直存在争议。最近，我们通过在小梁发育的关键阶段有条件地删除编码关键心脏转录因子的基因Nkx2-5，生成了新的LVNC小鼠模型。这些条件性突变小鼠重现了与LVNC患者相似的病理特征，包括左心室小梁增多伴心内膜深凹陷、心内膜下纤维化、传导缺陷、应变缺陷和进行性心力衰竭。在讨论了描述小梁心肌和致密心肌在心室形态发生过程中各自作用的最新发现后，本综述将重点关注反映小梁发育与LVNC之间联系的新数据。
