Science: The regulatory mechanism of mechanical stress on heart valve formation

The heart is the engine of life, continuously providing power in the circulatory system, and is one of the most critical and delicate organs in the living body

Recently, Julien Vermot's research group of the French National Institute of Health and Medical Research published an article entitled "Bioelectric signaling and the control of cardiac cell identity inresponse to mechanical forces" in "Science", describing the formation process of cardiovascular valves and mechanical The regulatory mechanism of stress in this process

Mechanical forces, such as fluid shear stress and tensile forces generated by blood flow and heartbeat, are widely present in the blood circulation

The researchers first used the zebrafish as a biological model to control the spatiotemporal mechanical stress parameters with high precision, and used fluorescent probes (Tg) to perform real-time imaging of the fluorescent Ca2+ sensor protein GCaMP7a expressed in EdCs to monitor and analyze endocardial cells.

Ca2+ oscillations are formed almost exclusively in the AV canal region of the AV valve (top)

Nuclear factor of activated T cells 1 (Nfatc1), a known Ca2+-sensitive transcription factor, has been found in previous studies to regulate endocardial-mesenchymal transition and heart valve morphology happen

To determine whether the Ca2+ oscillations observed in EdCs were force-responsive, the researchers used drugs (MS-222, p-amino) to stop the heartbeat of zebrafish.

Further, the researchers hope to examine the effects of changing mechanical forces by manipulating the mechanical stress at the vascular valve boundary

The magnetic beads were manipulated by magnetic tweezers to alter the mechanical force at the vascular valve boundary

Magnetic tweezers are used to manipulate the position of the magnetic bead, the position of the magnetic bead changes (top F) and the position of the calcium ion oscillation (bottom F)

So when the stress goes wrong, does it have an impact on valve morphogenesis and development? Valve-like clusters were observed near the magnetic beads 16-20 hours after intra-atrial bead implantation

Manually regulated mechanical forces lead to abnormal valve position

In addition, the researchers also found that ATP (adenosine triphosphate) activates Ca2+ signaling through the purinergic receptor P2X channel, resulting in Ca2+ influx

ATP regulates Ca2+ influx, and extracellular ATP analogs can significantly enhance Ca2+ influx

In the present study, the researchers identified ATP-Ca2+ as an extended regulatory channel formed in cardiovascular formation and valve development, through which hemodynamic mechanical forces can guide heart valve development

A mechanosensitive signaling pathway model for valve development

In conclusion, this work demonstrates that biological systems rely on multiple mechanosensitive pathways to precisely control the morphogenetic process, which is also a safeguard mechanism that enhances the robustness of mechanical force regulation and avoids cardiac ectopic valve formation, an evolution of life.

References:

[1] https://