A new step in the understanding of heart valve training
Nov. 28, 2017
The team of Julien Vermot is interested in cellular and molecular mechanisms in the formation of cardiac valves, which are essential to the functioning of the heart and the blood circulation. By studying the behavior of endocardial cells on the inner surface of the heart during the very early development of the valve, the researchers showed that the behavior of endocardial cells is unique and differs radically from the endothelial cells lining the endothelium, the internal surface of the blood vessels. Indeed, if endothelial cell migration is oriented by blood flow, the cells of the endocardium seem to be reorganized independently of the direction of the flow. The researchers hope that these results, published in Development on November 28, 2017, will advance understanding of the mechanisms of heart valve disease.
Shortly after the first heartbeat, blood flow is established in the cardiovascular system. It has long been observed in vitro that endothelial cells migrate in the opposite direction to this flow. What is more, the forces exerted by the blood flowing on the innermost layer of the cells of the heart, called the endocardium, also lead to coordinated cell movements.
In this study, Julien Vermot's team observed the movements of endocardial cells in the early stages of development of a zebrafish embryo in order to determine whether their behavior also dependent on the flow.
The researchers combined high-resolution in vivo imaging techniques, performed at the IGBMC imaging center, with cardiac blood flow modeling, performed by Francesco Boselli, an expert in fluid mechanics in the laboratory, in collaboration with the University of Illinois at Urbana-Champaign (USA). These analyses showed that a significant part of the cells of the endocardium converge towards the valve formation region. Analysis of the mathematical model shows that the convergence motions are correlated with directional mechanical cues generated by the periodic movements of the fluid rather than flux direction. This observation contrasts with the role previously attributed to flow in the behavior of endothelial cells during the development of blood vessels.
These results illuminate the unique nature of the cells of the endocardium compared to the endothelial cells and the importance the mechanical during the embryonic cardiac development. This work thus advances understanding of the formation of valves at the cellular scale in the embryo.
This study was financed by the ANR and the ERC.