Defects in Trabecular Development Contribute to Left Ventricular Noncompaction

Abstract

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.

Keywords: Compaction; Lineage tracing; Trabeculation; Ventricular conduction system; Ventricular noncompaction.