Vascular remodelling in the embryo
Vascular remodelling is a process which occurs when an immature heart begins contracting, pushing fluid through the early vasculature.
Physical cues such as pressure, velocity, flow patterns, and shear stress are known to act on the vascular network in a number of ways, including branching morphogenesis, enlargement of vessels in high-flow areas, angiogenesis, and the development of vein valves.
Promoting an active remodelling process in some cases could help patients recover faster and retain functional use of donated tissues.
Thus, increased understanding of this biomedical phenomenon could aid in the development of therapeutics or preventative measures to combat diseases such as atherosclerosis.
[3] Subsequently, Chapman in 1918 discovered that removing a chick embryo's heart disrupted the remodelling process, but the initial vessel patterns laid down by vasculogenesis remained undisturbed.
The chemical basis of morphogenesis," written in 1952 by mathematician and computer scientist Alan Turing advocated for various biological models based on molecular diffusion of nutrients.
[4] However, a diffusive model of vascular development would seem to fall short of the complexity of capillary beds and the interwoven network of arteries and veins.
[4][5] In 2000, Fleury proposed that instead of diffusive molecules bearing responsibility for the branching morphogenesis of the vascular tree, a long-range morphogen may be implicated.
Once contraction of the heart begins, vascular remodelling progresses via the interplay of forces resulting from biomechanical cues and fluid dynamics, which are translated by mechanotransduction to changes at cellular and genetic levels.
[7] These strands then undergo a process called lumenization, the spontaneous rearrangement of endothelial cells from a solid cord into a hollow tube.
[8] Inside the embryo, the dorsal aorta forms and eventually connect the heart to the capillary plexus of the yolk sac.
Even this early in the process of vasculogenesis, before the onset of blood flow, sections of the tube system may express ephrins or neuropilins, genetic markers of arterial or venous identities, respectively.
[8] Angiogenesis is generally responsible for colonizing individual organ systems with blood vessels, whereas vasculogenesis lays down the initial pipelines of the network.
[2] The first event of biomechanical-driven hierarchal remodelling occurs just after the onset of heart beat, when the vitelline artery forms by the fusion of several smaller capillaries.
Subsequently, side branches may disconnect from the main artery and reattach to the venous network, effectively changing their identity.
[11] They grafted sections of quail endothelial tubing which had previously expressed arterial markers onto chick veins (or vice versa), showcasing the plasticity of the system.
[10] This indicates that the system as a whole exhibits a degree of plasticity which allows it to be shaped by transitory flow patterns and hemodynamic signals, however genetic factors do play a role in the initial specification of vessel identity.
[2] Once the heart begins to beat, mechanical forces start acting upon the early vascular system, which rapidly expands and reorganizes to serve tissue metabolism.
These forces must be balanced to obtain an efficient energy state for low-cost delivery of nutrients and oxygen to all tissues of the embryo body.
[7] A low Womersley number means that viscous effects dominate flow structure and that boundary layers can be considered to be non-existent.
[7] Mechanotransduction may act either by positive or negative feedback loops, which may activate or repress certain genes to respond to the physical stress or strain placed on the vessel.
The cell "reads" flow patterns through integrin sensing, receptors which provide a mechanical link between the extracellular matrix and the actin cytoskeleton.
Once some critical number of sprouting tubes have migrated into a previously unoccupied area, a path called a fractal can be established between these two points.
[5] This model yields a structure which is more random at the tips than in the major lines, which is related to the fact that Laplacian formulations are stable when speed is negative with respect to pressure gradient.
[5] Another large component of the remodelling process is the disconnection of branched vessels, which then migrate to distal areas in order to supply blood homogeneously.
[5] Branching morphogenesis has been found to follow the dielectric breakdown model, in that only the vessels with sufficient flow will enlarge, while others will close off.
Cardiovascular disease remains one of the most common causes of death globally[22] and is often associated with the blockage or stenosis of blood vessels, which can have dramatic biomechanical effects.
By understanding the implication of increased shear stress on homeostatic regulators, alternative, less-invasive methods may be developed to treat vessel blockage.
Conversely, angiogenesis and vascular remodelling is an important aspect of wound healing and the long-term stability of tissue grafts.
Thus, the study of vascular remodelling may also provide important insight into the development of new techniques to improve wound healing and benefit the integration of tissues from transplants by lowering the incidence of rejection.
