Vascular remodelling in the embryo
Fused Heart Tube : By the 25th day of gestation, a "heart" is already pumping and circulating blood through a network of vessels. These initial heartbeats come from a very different organ than the one seen in an adult. The early heart is really only a simple tube twisted back on itself because there is not enough room to grow. However, by the 5th week, the twisted tube fuses and becomes a two-chambered heart with one atrium and one ventricle.
Vascular remodelling is a process which begins at day 21 of human embryogenesis, when an immature heart begins contracting, pushing fluid through the early vasculature. This first passage of fluid initiates a signal cascade based on physical cues including shear stress and circumferential stress, which is necessary for the remodelling of the vascular network, arterial-venous identity, angiogenesis, and the regulation of genes through mechanotransduction. This embryonic process is necessary for the future stability of the mature vascular network.
Vasculogenesis is the initial establishment of the components of the blood vessel network, or vascular tree. This is dictated by genetic factors and has no inherent function other than to lay down the preliminary outline of the circulatory system. Once fluid flow begins, biomechanical and hemodynamic inputs are applied to the system set up by vasculogenesis, and the active remodelling process can begin.
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. The mechanotransduction of these physical cues to endothelial and smooth muscle cells in the vascular wall can also trigger the promotion or repression of certain genes which are responsible for vasodilation, cell alignment, and other shear stress-mitigating factors. This relationship between genetics and environment is not clearly understood, but researchers are attempting to clarify it by combining reliable genetic techniques, such as genetically-ablated model organisms and tissues, with new technologies developed to measure and track flow patterns, velocity profiles, and pressure fluctuations in vivo.
Both in vivo study and modelling are necessary tools to understand this complex process. Vascular remodelling is pertinent to wound healing and proper integration of tissue grafts and organ donations. Promoting an active remodelling process in some cases could help patients recover faster and retain functional use of donated tissues. However, outside of wound healing, chronic vascular remodelling in the adult is often symptomatic of cardiovascular disease. Thus, increased understanding of this biomedical phenomenon could aid in the development of therapeutics or preventative measures to combat diseases such as atherosclerosis.
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